【Abstract】Objective To establish a C57BL/6J mouse model of alopecia areata (AA) induced by imiquimod (IMQ) and cyclophosphamide (CTX) and compare its characteristics. Methods 104 C57BL/6J mice were divided into an IMQ group (applying 5% 0.05 g IMQ to the head/back, 4 times a week, for 4 weeks) and a CTX group (intraperitoneal injection of 3 mg/20 g CTX after hair removal). The control group was treated with Vaseline (0.05 g) or only hair removal in the corresponding area. During the modeling process, continuously monitor the changes in body weight and hair of mice. HE staining was used to observe changes in skin hair follicles and epidermal thickness. The Elisa method was used to detect the levels of interferon - γ (IFN-γ), interleukin-15 (IL-15), and tumor necrosis factor - α (TNF-α) in mouse head and back skin lesions and serum. Results The IMQ modeling cycle is about 4 weeks, and in the fourth week, a patchy bare area with an area of about 1 cm × 1 cm is formed at the head and back skin lesions, accompanied by a small amount of scales; The modeling cycle of CTX is about 14 days. After intraperitoneal injection of CTX for 5 days, the hair on the head and back lesions falls off, and the skin appears dark gray. Histopathology showed significant changes in hair follicles between the two model groups of mice compared to the control group, with the IMQ model group showing more significant thickening of the epidermis. Both IMQ and CTX modeling methods can significantly increase IFN-γ, IL-15, and TNF-α in skin tissue and serum, with the IMQ modeling method showing a more pronounced increase in inflammatory factors. Conclusions Both IMQ and CTX can successfully induce alopecia areata models in the head and back of C57BL/6J mice. Compared with IMQ modeling, CTX modeling has the advantages of shorter modeling time, higher survival rate, and higher modeling rate, making it a relatively stable AA animal modeling method.