Objective To prepare and evaluate the animal model of rheumatoid arthritis with depression (RAD). 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 8 rats in each group. The N group was fed normally, while the D group was fed solitary rearing for 1 week and chronic unpredictable mild stress (CUMS) for 3 weeks, RA group was induced by collagen-induced arthritis (CIA) to establish the arthritis model. In RAD group, RAD animal model was established on the basis of CIA animal model, meanwhile, adding 1 week solitary rearing and 3 weeks CUMS. Toe volume, arthrits index (AI), Synovial and ankle joint pathology, 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 rheumatoid arthritis 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, number of standing uprights), serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), and pathological changes of hippocampus. The RAD animal model was successfully prepared if depression and rheumatoid arthritis were both tested in the rats. Results Compared with the N group, toe volume, AI score and the levels of IL-1β, IL-6 in serum of RA group and RAD group were significantly increased (P＜0.05 or P＜0.01), the joint space widened, synovial hyperplasia was obvious and extended to the joint cavity, and a large number of inflammatory cells were seen; in D group and RAD group, body weight, food intake, total number of motion cells, number of standing uprights and sugar water preference rate of rats were decreased to different degrees, and the levels of CRH, ACTH, CORT in serum were increased in different degrees (P＜0.05 or P＜0.01), the neuron cells arranged loosely, gap increased, the number decreased, accompanied by some nucleus pyknosis, dissolution, rupture, especially in the model group. Conclusion CIA combined with solitary rearing and CUMS can better simulate the changes in the external manifestations and internal indicators of RAD model animals, which can provide reference for the study of RAD disease animal models.