Objective To establish and evaluate an animal model of rheumatoid arthritis with depression. Methods Thirty-two rats were randomly divided into normal group (N group), depression group (D group), arthritis group (RA group) and model group (RAD group), with eight rats in each group. The N group was fed normally, and the D group was fed under solitary rearing for 1 week and chronic unpredictable mild stress (CUMS) for 3 weeks. The RA group was subjected to collagen-induced arthritis (CIA) to establish the arthritis model. In the RAD group, the RAD animal model was established on the basis of the CIA animal model with 1 week of solitary rearing and 3 weeks of CUMS. Toe volume, arthritis index (AI), synovial and ankle joint pathology, and serum levels of interleukin-1β(IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were used to evaluate whether the rat model of RA was successfully established. The depression status of rats was evaluated by measuring body weight, food intake, sugar water preference rate, open field behavior (total number of motion cells and number of standing uprights), serum levels of corticotropin-releasing hormone ( CRH), adrenocorticotropic hormone ( ACTH), and corticosterone ( CORT), and pathological changes in the hippocampus. The RAD animal model was successfully established when both depression and RA were present in the rats. Results Compared with the N group, the toe volume, AI score, and serum levels of IL-1β and IL-6 in RA and RAD groups were significantly increased (P< 0. 05), joint space had widened, synovial hyperplasia was obvious and extended to the joint cavity, and a large number of inflammatory cells were seen. In D and RAD groups, body weight, food intake, total number of motion cells, number of standing uprights, and sugar water preference rate were decreased by various degrees, serum levels of CRH, ACTH, and CORT were increased by various degrees, and neuronal cells were reduced, accompanied by partial nuclear atrophy, especially in the model group (P< 0. 05). Conclusions CIA combined with solitary rearing and CUMS better simulates the changes in external manifestations and internal indicators of RAD model animals, which provides a reference to study RAD disease animal models.