Objective: To investigate pathological changes of the cartilage and concentrations of interleukin-1β (IL-1β) in blood and matrix metalloproteinases (MMPs) in joint fluid with lappaconitine treating on rabbit knee osteoarthritis model copied by Hulth surgery. Methods: 42 New Zealand rabbits are copied osteoarthritis model by Hulth surgery, 6 animals were killed randomly 4 weeks later to be tested under microscope, and the remaining 36 rabbits were randomly divided into treatment group and model group, 0.5ml?kg-1 weight of intra-articular injection of lappaconitine with treatment group once a week for 4 weeks. The model group were given the same dose of saline. After 4、6、8 weeks, six animals were killed in the 2 groups respectively to take out tissue of the medial femoral condyle to make slice and HE staining to observe chondrocytes morphology, meanwhile, concentrations of IL-1β、MMP-2 were tested. Result: Compared to the model group, the Mankin’s score in treatment group is significantly lower(P <0.01) in 6 week, much significantly lower(P <0.001) in 8 week. The concentration of MMP-2 in joint fluid was lower in 4 week (P <0.05) and was significantly lower in 6 week(P <0.01). Conclusion: lappaconitine can reduce the concentrations of MMP-2 in joint fluid and protect the articular cartilage in arthritis. [Keywords] Lappaconitine; knee osteoarthritis; inflammatory cytokines