A series of flashbacks reveal that only Yoki survived, coming under the care of Nui, who is a Mushishi (or Bugmaster)—an expert in Mushi, which are supernatural bug-like creatures that are invisible to most humans.

After he helps the locals, Ginko is asked by the innkeeper to look at her granddaughter, Maho, who is deaf, has horns on her forehead, and hears strange noises.

[3] Initially, producer Satoru Ogura came up with the idea of making a jidaigeki in collaboration with the team that worked on Crouching Tiger, Hidden Dragon.

[1] Otomo was not confident in working on "a project of that size" as he had only directed one live-action film in 1991, titled World Apartment Horror.

[1][2] He instead suggested adapting Mushishi as he felt it would be "an opportunity to mix live action and computer graphics, to create a hybrid of the natural and the virtual".

He found the episodic nature of the work challenging but was able to fashion a cohesive screenplay by combining elements of the different stories present in the manga.

Otomo describes the film as "a kind of fable", and as such, he chose the Meiji era as its setting because he felt it offered the best framing for the story, as he considered the sudden disappearances of certain characters were also consistent with the nature of that historical period.

[4][21] On its exhibition at the Sundance Film Festival, all tickets were sold out, and some people watched it standing because they did not buy reserved seats.

[23] Anime News Network's Bamboo Dong praised its visuals but noted that the film could be confusing for viewers who are unfamiliar with the manga series and that Ginko "looks more like a cosplayer".

[24] Tony Sullivan of Eye for Film said it is "beautifully acted, shot and scored" but cited the "lack of oomph" as a reason why "the movie is rather dull".

[25] Mark Schilling from The Japan Times praised Odagiri but criticized the film for being "a text too tangled and murky for the uninitiated to easily penetrate or parse".

[26] The cast performance was praised by Variety reviewer Derek Elley who declared its "longueurs and narrative obscurities consign this 'Bug' to highly specialized outings".

[25][26][27] Sally Foster from Film Threat praised its visuals and "a few good Japanese-style creep-out scenes" but described the storyline as "incomprehensible" due to "the overabundance" of information about its mythology.

[28] John Sinnott of DVD Talk asserted the film could not reach the quality of the manga; he cited the lack of explanation about Ginko's background as one of the reasons.

[29] While praising Odagiri's acting and deeming the film's visuals an "A-game", DVD Verdict's Adam Arseneau said it "feels disjointed and fragmented".

[30] While he preferred the anime version, Mania.com's Chris Beveridge praised the film as "a soothing and atmospheric movie that captures everything that it should", singling out Otomo's direction and Odagiri's acting.