The cast includes such Lynch regulars as Laura Dern, Justin Theroux, Harry Dean Stanton, and Grace Zabriskie, as well as Jeremy Irons, Karolina Gruszka, Peter J. Lucas, Krzysztof Majchrzak, and Julia Ormond.

There are also brief appearances by a host of additional actors, including Nastassja Kinski, Laura Harring, Terry Crews, Mary Steenburgen, Diane Ladd, and William H. Macy.

The film's cinematography, editing, score, and sound design were by Lynch, with pieces by a variety of other musicians also featured, including Beck, Nina Simone, Kroke, Dave Brubeck, and Krzysztof Penderecki.

[13][14] A crackling vinyl record announces that "Axxon N., the longest-running radio play in history", is turning to "a gray winter day in an old hotel".

She watches an old Eastern European woman approaching a mansion, but flips to a television show about a family of surrealistic anthropomorphic rabbits.

In Los Angeles, actress Nikki Grace is waiting for the results of her audition for the lead role in the film On High in Blue Tomorrows, a romantic drama about two people who have an affair.

She asks Nikki about the film and then tells "an old tale": a boy passed through the doorway into the world, causing a reflection that gave birth to an evil that followed him.

Shaken, the director confesses that they are shooting a remake of an unfinished German film entitled 47, itself based on a supposedly cursed Polish folktale.

Nikki walks into an alley and enters a door named "Axxon N." It leads to the On High in Blue Tomorrows set, but also takes her back in time.

In a daze, Nikki wanders off set and into a nearby cinema, where she sees not only On High in Blue Tomorrows but events occurring in real-time.

The film ends with a celebration involving the troupe of prostitutes, a one-legged woman mentioned earlier, Niko and her pet monkey, and others.

Its structure is more akin to a web where individual moments hyperlink to each other and other Lynch films—hence the musical number that closes the film which contains obvious allusions to everything from Blue Velvet to Twin Peaks.

When asked about Inland Empire, Lynch refrained from explaining the film, responding that it is "about a woman in trouble, and it's a mystery, and that's all I want to say about it.

[17][18]Lynch's Darkened Room has been analyzed by Kristina Šekrst as a precursor to Inland Empire, creating the Lost Girl motif, along with sharing the same symbolism of the cigarette-burn hole in a silk slip and the watch.

"[16] The Guardian critic Peter Bradshaw called the film "a meditation on the unacknowledged and unnoticed strangeness of Hollywood and movie-making in general", adding that Lynch "establishes a bizarre series of worm-holes between the worlds of myth, movies and reality.

[21] He also commented that "to see Lynch's worlds captured on digital video makes for a bizarre short-circuiting: as if we are witnessing a direct feed from the unconscious".

[21] Dennis Lim of Slate described the film as "a three-hour waking nightmare that derives both its form and its content from the splintering psyche of a troubled Hollywood actress", and commented on Lynch's use of digital video, describing it as "the medium of home movies, viral video, and pornography—the everyday media detritus we associate more with ... intimate or private viewing experiences than communal ones", adding that the film "progresses with the darting, associative logic of hyperlinks".

[22] Scholar Anne Jerslev has argued that the film "constitutes multiple and fractured modes of perception in a world of digital screens".

[23] Jerslev further contends that the film features "formal similarities with a website's hyperlinked layering of screens/windows, constantly disclosing new worlds from new points of view", but according to theorist Steven Shaviro "it also builds on cinematic codes, even as it deconstructs them".

He connects this theme to Lynch's interest in Theosophy and draws parallels with James Joyce's Ulysses and the Netflix series The OA, highlighting shared motifs of reincarnation and alternate lives.

[24] The Austin Chronicle's Marc Savlov wrote that Inland Empire "revels in a kind of post-9/11 disassociative disorder as perpetual panic attack".

[32] Instead, it premiered at Italy's Venice Film Festival on 6 September 2006, where David Lynch also received the Golden Lion lifetime achievement award for his "contributions to the art of cinema".

[35] He acquired the rights to the DVD and worked out a deal with StudioCanal in an arrangement that allowed him to distribute the film himself, through both digital and traditional means.

Among other special features, the DVD included a 75-minute featurette, "More Things That Happened", which compiled footage elaborating on Sue's marriage to Smithy, her unpleasant life story, the Phantom's influence on women, and the lives of the prostitutes on Hollywood Boulevard.

Lynch contributed a number of his own compositions to the film's soundtrack, marking a departure from his frequent collaborations with composer Angelo Badalamenti.

The following month, he announced his intent to self-distribute the film theatrically via his company Absurda and 518 Media, stating, "A conventional distributor is a heartache, and I’m finished with that.

Lynch embarked on a 10-city promotional tour in January 2007 with a cow, explaining "I ate a lot of cheese during the film, and it made me happy.

The website's critical consensus reads, "Typical David Lynch fare: fans of the director will find Inland Empire seductive and deep.

[46] Peter Travers, the film critic for Rolling Stone magazine wrote, "My advice, in the face of such hallucinatory brilliance, is that you hang on.