Since her debut, Mrs. Brisby has been mostly positively received for her timid personality combined with her kindness and courage, with critics citing her as a unique representation of a mother character who braves through an actively hostile world to save her children.

Because her son, according to the doctor mouse, Mr. Ages, was gravely ill and therefore could not survive having to travel out of his home, Mrs. Frisby must seek help from an old owl, and the bird informed her to seek out an intelligent rodent group called the "Rats of NIMH" (abbreviation of National Institute of Mental Health) so that they could help to relocate Mrs. Frisby's house and thereby save Timothy and the other children.

[4] Bluth, in his autobiography, praised the story told in Mrs. Frisby and the Rats of NIMH, speculating that Walt Disney would have adapted it into a movie if O'Brien contacted him while both were still alive.

[4] Bluth wrote that the "timid yet brave Mrs. Frisby" reminded him of his grandmother because she worked hard to care for her thirteen children and always advised him whenever he visited her as a child, "Whatever problem you have, just put your shoulder to that wheel and go forward.

The film's smooth animation was combined with large amounts of lighting plus shading to convey different tones, such as the suspense that was built up when Mrs. Brisby visited the Great Owl.

[12] Mrs. Brisby was likely difficult to animate due to her delicate gestures consistent with her timid personality, which were in contrast to the more exaggerated movements of her friend, a comedic crow named Jeremy.

[14] Bluth recalled that Hartman "read the lines with an ever-so-slight tremble to her voice, turning Mrs. Brisby into a timid and unsure character," making the fictional mouse easier to sympathize with.

He thought that Hartman was cleverly reading Brisby's lines but eventually realized that her voice acting reflected her depression in reality when he learned that the actress took her own life in 1987.

She enters the rose bush and meets different members of the Rats of NIMH including Captain Justin, Jenner, and their leader, Nicodemus.

Nicodemus informs Mrs. Brisby of her husband's contributions in helping the rats escape from the institution NIMH and gives her a red amulet that is powered by the wearer's courage.

Overhearing that NIMH members are arriving to kill the residential rats, she escapes from her cage to warn her fellow rodents to leave their area.

[6][15] Tyler B. Searle of Collider attributed the acclaimed story of The Secret of NIMH to Brisby's personality, calling her "one of the greatest portrayals of the power of motherhood in cinema.

"[19] Because of her generally likable personality, combined with the harsh challenges she faces, writers of multiple publications have stated that audiences could identify with the character to the point of rooting for her and celebrating her successes.

[7][20] 411MANIA author Aaron Hubbard praised the story for taking advantage of the "sympathetic" Brisby being "small and kind of helpless" as a mouse but progressing through major obstacles thanks to her "great resolve and inner strength.

"[15] Critics of multiple newspaper publications that date to 1982 appreciated that while Mrs. Brisby is a shy and timid individual that she is able to muster up strength and courage over the course of her journey.

[8] Film Inquiry co-writer Aaron Berry called her "adorable" and his favorite movie hero because she is neither "the biggest [n]or strongest, but the one who will go out of their comfort zone and go even further to keep what they could risk losing.

"[10] Jesse Hassenger of Fox 29 attributed the film's narrative success to Mrs. Brisby being "the whole movie" instead of a "disposable plot engine" who could be written off to spotlight her children.

[29] Neil Sharpson explained that he found Mrs. Brisby to be a unique character with no modern film protagonist analogues in that she is not a conventionally "strong" or wisecracking hero, but one who endures an actively hostile world because she "is not fearless, she is brave.

"[26] In an academic journal, the author Hannah Sophie Schiffner noted that Mrs. Brisby was amongst the rising trope of heroic mice in children's films from the late 1970s onwards who have enough character agencies to challenge societal norms.