Abstract: Objective To establish a novel animal model of trichomadesis with C3H/HeJ mice induced by imiquimod, so as to provide a new experimental platform for human alopecia areata study. Methods Fifty-eight C3H/HeJ mice were divided into 7 groups. The mice in the experimental groups 1 - 5 were treated with topical application of imiquimod on the neck thrice a week, twice a week, and once a week, on the back thrice a week, on the abdomen thrice a week, respectively, for various durations. Vacant vehiculum was given to the mice in control group 1 for 10 weeks, and no intervention to the control group 2. The mice were observed for the occurrence of trichomadesis. Immunohistochemistry was used to detect the distribution of CD4+, CD8+ T cells around follicles, in situ hybridization to examine the mRNA expression of IFN-γ in perifollicular cells. Results The total effective rates of induction of trichomadesis were 100%, 100%, 40%, 67%, 50% in the experimental groups 1-5, respectively. The difference between experimental group 1 or 2 and the others was significant （P < 0.05）. The aggregation of CD4+ T and CD8+ T cells as well as the high expression of IFN-γ mRNA were also observed in cells around the follicles in the area of trichomadesis induced by imiquimod （both P < 0.05）. Conclusion Imiquimod could induce the occurrence of trichomadesis in C3H/HeJ mice with extreme resemblance to human alopecia areata in both clinical manifestations and pathology.