Objective To observe the effects of paeonol on collagen induced arthritis (CIA) and investigate its mechanisms. Methods The tentative arthritis mice model was created by injecting type Ⅱ collagen. The severity degree of RA was scored according to the rating criteria after treatment with paeonol. ELISA method was employed to detect the levels of IL-12, TNF-2, IFN-γ and anti-type Ⅱ collagen autoantibody. The efficacy of paeonol was compared with that of MTX (the positive control) and PBS was used as the negative control. Results We found that paeonol could alleviate severe RA, inhibit the expression of inflammatory cytokines such as IL-12, TNF-2, IFN-γ and reduce the level of anti-type Ⅱ collagen autoantibody in serum, which was similar with MTX. Conclusion The results show that paeonol has a reliable therapeutic effect for RA. This study has provided a good clue for the future research and development of medications for the treatment of RA.