Objective:To explore the method of animal model building of knee osteoarthritis based on joints’ mechanical instability  Methods:Twenty-four New Zealand white rabbits were randomly divided into three groups:normal group, 4 weeks model group and 8 weeks model group, with 8 rabbits in each group. The animals of model groups were making osteoarthritis models by operation, with medial collateral ligament (MCL) cutting off and resection of part of patellar ligament. The rabbits in normal group were only operated by skin incision and exposure of ligaments mentioned above. Animals were sacrificed at 4 and 8 weeks after operation in each group, and the serum and knees of each rabbit were taken at the same time. After HE staining, the morphological structure of articular cartilage was observed by microscope and Mankin’s score was made according to the degree of cartilage degeneration. The expressions of IL-1β, TNF-α and MMP-13 in serum were detected by immunohistochemical techniques  Results:The degeneration in varying degrees was observed in articular cartilage from 4 weeks model group and 8 weeks model group, whose Mankin’s scores were significantly higher than the samples of normal group (P<0.01). Comparing with the normal group, the level of IL-1β, TNF-αand MMP-13 in serum were higher from the rabbits both of 4 weeks model group and 8 weeks model group statistically (P<0.01)  Conclusion:The modeling method by cutting off MCL as well as excision of part of patellar ligament could provide an ideal animal model of knee osteoarthritis, with the advantages of simple operation, low rates of infection and mortality.