In this study, a collagen-induced arthritis (CIA) model was established to simulate rheumatoid arthritis (RA) using two intradermal injections of bovine type H collagen and Freund's complete adjuvant mixture given at two-week intervals. Subsequently, the transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) was used to treat RA and the treatment efficacy, as well as the possible regulatory mechanism underlying hUC-MSC transplantation, was observed. During the study, forty rats were randomly divided into four groups and their blood samples were collected at different time points to measure levels of serum cartilage oligomeric matrix protein (COMP). Based on the symptoms and pathological features of the rats, a total success rate of 83% was achieved by the treatment. Furthermore, the improvement of joint symptoms was more obvious when methotrexate and MSC transplantation were used. In summary, it was concluded that MSC transplantation relieved the symptoms of arthritis by down-regulating the expression of COMP on the synovial membrane and in the serum of CIA rats.