Objective To establish and compare C57BL / 6J mouse models of alopecia areata induced by imiquimod (IMQ) and cyclophosphamide (CTX). Methods A total of 104 C57BL / 6J mice were divided into an IMQ group (5% 0. 05 g IMQ applied to the head / back, 4 times a week, for 4 weeks), a CTX group (intraperitoneal injection of 3 mg / 20 g CTX after hair removal), and a control group treated with Vaseline (0. 05 g) or hair removal alone in the corresponding area. Body weight and hair changes were monitored continuously during the modeling process. Changes in skin hair follicles and epidermal thickness were observed by hematoxylin-eosin staining.Expression 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 were detected by enzyme-linked immunosorbent assay. Results The IMQ group cycle was 4 weeks, and a patchy bare area about 1 cm × 1 cm developed on the head and back skin in week 4,accompanied by a small amount of scales. The CTX modeling cycle was 14 days, and the hair on the head and back lesions fell off 5 days after intraperitoneal CTX injection, and the skin appeared dark gray. Histopathology showed significant changes in hair follicles between the two model groups compared with the control group, with greater thickening of the epidermis in the IMQ group. Both IMQ and CTX significantly increased IFN-γ, IL-15, and TNF-α levels in skin and serum(P< 0. 0001), with a more pronounced increase in inflammatory factors in the IMQ group (P<0. 0001, P<0. 001, P<0. 01). Conclusions Both IMQ and CTX can successfully induce alopecia areata on the head and back in C57BL / 6J mice. Compared with IMQ, CTX modeling has the advantages of shorter modeling time,higher survival rate, and higher modeling rate, creating a relatively stable animal model of alopecia areata.