Objective：To investigate the improvement of cartilage damage and immunomodulatory effects of osthole on type Ⅱ collagen-induced arthritis rats. Methods：A rheumatoid arthritis rat model was inducd by bovine type Ⅱ collagen. Osthole was administered by intragastric injection one week after the modeling was established. The paw volume of each group and the arthritis index were evaluated every 4 days. After 30 days，the spleen index and thymus index were determined by weighing method. Cartilage damage was observed by HE staining. The levels of IL-1β，IL-6 and TNF-α in peripheral blood were measured by ELISA. The expressions of MMP-1，MMP-3 and MMP-13 mRNA were determined by qRT-PCR. The levels of Ki67，PCNA，Caspase-3，Caspase-9，MMP-1，MMP-3，MMP-13，Wnt 1，β-catenin and LRP5 were detected by Western blot. Results：Compared with the model group，the paw volume，arthritis score，spleen index and thymus index of the osthole treated group were decreased，the degree of chondrocyte arrangement disorder and inflammatory cells were reduced，the expressions of Ki67 and PCNA were up-regulated，and Caspase-3 and Caspase-9 were down-regulated，the contents of IL-1β，IL-6 and TNF-α were decreased，the expressions of MMP-1，MMP-3，MMP-13，Wnt 1，β-catenin and LRP5 were down-regulated，and the effects were greatest in the Ost 40 mg/kg group（P < 0.01）. Conclusion：Osthole can alleviate cartilage damage，inflammation，and destruction of collagen in the articular cartilage matrix of rats with rheumatoid arthritis，which may be achieved by inhibiting the activation of the Wnt signaling pathway.