Objective To establish an imiquimod compound chronic unpredictable mild stress ( CUMS) C57BL/6J mouse model of alopecia areata (AA). Methods Thirty female C57BL/6J mice aged 5 ~ 7 weeks were randomly divided into three groups of 10 mice each: control, IMQ, and CUMS (imiquimod combined with CUMS) groups. CUMS was administered to the CUMS group on days 1 ~ 21, whereas IMQ and CUMS groups were administered equal amounts of imiquimod cream topically at the same site on days 14 ~ 21. On day 21, overall and trichoscopic photographs of mice were taken, behavioral tests were performed, and skin lesions and peripheral blood were collected. CD4P>+P> and CD8P>+P> T cell infiltration into hair follicles was observed by immunohistochemical staining. Differentiation of Th1/ Th2 and Th17/ Treg cells from peripheral blood T lymphocyte subsets was detected by flow cytometry. Results Compared with blank and imiquimod groups, C57BL/6J mice in the CUMS group showed significant localized patchy hair loss, and trichoscopic photographs showed broken hair and exclamation mark-like hairs. The distance moved, number of times standing upright, and number of times entering the central area in the open field test were significantly reduced (P< 0. 05). Moreover, the rest time in the forced swim test was significantly increased (P< 0. 05). These data suggested that the mice were in an anxious and depressed state. Compared with blank and imiquimod groups, CUMS group mice had significant CD4P>+P> and CD8P>+P> T cells in skin lesions around hair follicles and in the hair follicle bulb. Flow cytometry showed that Th1 levels were significantly higher (P< 0. 01), Th2 levels were significantly lower (P< 0. 05), Th17 levels were significantly higher (P< 0. 05), the Th1/ Th2 ratio was significantly higher (P< 0. 001), and the Th17/ Treg ratio showed an upward trend in the CUMS group. Conclusions The C57BL/6J mouse model established by topical imiquimod combined with CUMS essentially simulates human AA manifestations. This method highlights the psychosomatic factors in AA pathogenesis, and to some extent, conforms to liver depression and spleen deficiency syndromes in TCM, providing a cultivation-friendly and more cost-effective modeling method for basic research of AA.