Objective:To observe the intervention effects of Chinese medical manipulation on the articular cartilage degeneration in rabbit model of knee osteoarthritis,and explore its mechanism from the perspective of cell signaling transduction. Methods24 New Zealand white rabbits were randomly divided into the normal group,model group and manipulation group. Except the normal group,the model of knee osteoarthritis was established by operation in the other two groups. After modeling for 4 weeks,the manipulation group was treated with manipulation therapy such as patella massage and joint passive flexion and extension. After intervention for 8 weeks,the rabbits were sacrificed and the knee joints were exposed for morphological observation. The femoral condyle was collected and made into pathological sections for HE staining. The histopathological features were observed under microscope and evaluated by Mankin’s score,and the degeneration of articular cartilage in each group was compared. The mRNA expression levels of IL-1β、iNOS and MMP-13 in synovial tissues and P38 as well as ERK1/2 in cartilage tissue were detected by RT-PCR. The protein expression levels of MMP-13 and phosphorylated ERK1/2(p-ERK1/2)in cartilage tissue were detected by Western-blot. All the experimental data were compared and conducted the statistical analysis.  Results:The degree of articular cartilage degeneration in the manipulation group was obviously alleviated compared with the model group,and the Mankin’s score in the manipulation group was significantly lower than that in the model group (P<0.05). Compared with the model group,the mRNA expression levels of P38 and ERK1/2 in cartilage and IL-1β,iNOS and MMP-13 in synovial tissues in the manipulation group were significantly down-regulated (P<0.05). Compared with the normal articular cartilage,the protein expressions of MMP-13 and p-ERK1/2 were significantly up-regulated in the model group and manipulation group. While the protein activation degree of MMP-13 and p-ERK1/2 in the manipulation group was obviously inhibited compared with that in the model group.  Conclusion:Chinese medical manipulation can effectively inhibit the cartilage degeneration degree of knee osteoarthritis,and affect the expressions of inflammatory mediators and cytokines. Its mechanism may be associated with inhibition of mitogen-activated protein kinase(MAPK)signal transduction pathway in articular cartilage.