Abstract: OBJECTIVE To observe the microstructure and the expression of related proteins of articular cartilage in the knee osteoarthritis rats, which were treated with Yougui pill, and to further reveal its mechanism. METHODS Sixty SD rats were randomly divided into six groups:sham operation group, model group, glucosamine sulfate group, Yougui pill(high-dose, middle-dose and low-dose) group, 10 rats in each group. The modified Hulth method was used to make KOA models for 6 weeks. The rats were gavaged with corresponding drugs for 8 weeks. The morphological change of cartilage was observed by HE staining, it was evaluated by Mankin score. The expression of heat shock protein 90a(Hsp90a), calmodulin(CaM), calmodulin kinase-Ⅱ(CaMK-Ⅱ), myosin phosphatase Rho-interacting protein(Mprip) was analyzed by immunohistochemistry. The expression of Hsp90α was checked by Western blotting. RESULTS Compared with the sham operation group, the Mankin score was obviously raised in the model group, the protein expression of Hsp90α was evidently increased in the model group, the protein expression of CaM and Mprip was evidently decreased in the model group(P<0.05), articular cartilage was seriously damaged, and chondrocytes were arranged in disorder. Compared with the model group, the Mankin score and the expression of Hsp90α were declined obviously in the high-dose Yougui pill group, but the protein expression of CaM and Mprip was evidently increased in the high-dose group(P<0.05), cartilage structure was tended to be normal, the chondrocytes distribution was uneven, and articular cartilage surface was not smooth. CONCLUSION Yougui pill is effective for delaying articular cartilage degeneration. Yougui pill can regulate calcium metabolism by up-regulating the expression of Mprip and CaM and down-regulating the expression of Hsp90α.