Abstract: [Objective] To explore the mechanism of curcumin in the treatment of pain and cartilage degeneration in rats with knee osteoarthritis (KOA). [Methods] 30 male SD rats were randomly divided into sham operation group (S group), model group (M group) and curcumin group (C group) with 10 rats in each group. The model was made by cutting off the anterior cruciate ligament of the right knee.C group was given intraperitoneal injection of curcumin (50mg/kg), S group and M group were given the same amount of DMSO once a day for 8 weeks. The mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), SO staining, the content of IL-1 β, TNF- α, MCP-1 and the protein expression of MMP-1, MMP-13, Collagen Ⅱ and Aggrecan were compared in each group. [Results] MWT and TWL in M group were significantly lower than those in S group, while MWT and TWL in C group were significantly higher than those in M group. The contents of IL-1 β, TNF- α and MCP-1 in M group were significantly higher than those in S group, while the contents of IL-1 β, TNF- α and MCP-1 in C group were significantly lower than those in M group (P<0 05). The results of SO staining and OARSI score showed that the degeneration of cartilage in M group was more severe than that in S group, while that in C group was significantly less than that in M group. Compared with S group, MMP-1 and MMP-13 protein in M group increased significantly, while CollagenⅡ and Aggrecan protein decreased significantly. Compared with M group, MMP-1 and MMP-13 protein in C group decreased significantly, while CollagenⅡ and Aggrecan protein increased significantly. [Conclusion] Curcumin can significantly reduce the hyperalgesia and cartilage degeneration of KOA in a rat model, and its mechanism may be related to the reduction of the contents of IL-1 β, TNF- α and MCP-1 and the restoration of cartilage metabolic balance.