Objective To investigate the effect of Cinnamaldehyde on type Ⅱ collagen-induced arthritis（CIA） in rats and on the levels of osteopontin (OPN). Methods We selected 20 healthy SPF SD rats, and randomly selected 5 rats as the control group. The remaining rats were used to establish CIA model. We randomly divided the rats with successful modeling into a model group, a low-dose Cinnamaldehyde group, and a high-dose Cinnamaldehyde group, with five rats in each group. After successful modeling, rats were administrated continuously for 3 weeks, once a day. The low-dose Cinnamaldehyde group and the high-dose Cinnamaldehyde group were treated with 100mg/kg and 200mg/kg Cinnamaldehyde intragastrically, respectively. The normal group and the model group were treated with the same amount of normal saline intragastrically. The effect of Cinnamaldehyde on arthritis score of CIA rats was observed. That levels of OPN, IL-6, IL-17 and TNF-α in serum of rats from each group were detected. OPN expression in synovial tissue was detected by immunohistochemistry（IHC）, OPN protein expression in synovial tissue was detected by Western blot, OPN mRNA level in cartilage was detected by RT-QPCR, and pathological changes in joint tissues of rats in each group were observed by HE staining. Results Compared with the control group, the arthritis score of rats in the model group was significantly increased, the serum levels of OPN, IL-6, IL-17 and TNF-α were significantly increased, the expression levels of OPN in synovial membrane and cartilage were increased, and the joint tissues showed significant inflammatory cell infiltration and synovial hyperplasia. Compared with the model group, the low-dose Cinnamaldehyde group and the high-dose Cinnamaldehyde group could reduce the arthritis score of rats, significantly reduce the levels of OPN, IL-6, IL-17 and TNF-α in serum, and reduce the expression levels of OPN in synovial membrane and cartilage, as well as alleviate the pathological damage of joint tissues. The effect of the high-dose Cinnamaldehyde group was more significant. 〖WTHZ〗Conclusion Cinnamaldehyde can effectively alleviate joint inflammation and joint injury in CIA rats, which may be related to the reduction of OPN expression and the reduction of serum levels of IL-6, IL-17 and TNF-α