Objective To investigate the effects of compound cornu cervi degelatinatum on the expression of related inflammatory cytokines and pathological changes of the synovium in mice with collagen-induced arthritis (CIA). MethodsThe CIA model of Balb/c mice was established. The mice were randomly divided into 5 groups: blank control group, model control group, low-dose group ( C1 ) , high-dose group ( C2 ) and glucosidorum tripterygll totorum group D. After the first immunization in mice, we observed the general condition and lesions of the fore and hind jaws. After the second immunization, the mice in groups C1 and C2 were orally administered with compound cornu cervi degelatinatum at the doses of 2. 5 and 5 g·kg-1 body weight per day for 4 weeks, and meanwhile those in group D were administrated with glucosidorum tripterygll totorum at the dose of 13. 6 mg·kg-1 body weight per day. The serum of the mice was collected to detect the levels of TNF-αand IL-4 by ELISA. Ankle joints were harvested, and the pathological changes of synovial tissues were observed under light microscope. Results As compared with the model control group, the level of TNF-αin the treatment groups was significantly decreased, while the level of IL-4 was elevated in group C1. Histological pathology of ankle joints demonstrated that the synovium of the CIA mice were hyperplastic and the synovial tissues were markedly ameliorated in treatment groups. Conclusion The compound cornu cervi degelatinatum can relieve redness and swelling in mice with CIA. The mechanism may be related to the inhibition of pro-inflammatory cytokine TNF-α and regulation of anti-inflammatory cytokine IL-4.