To examine the expression of MMP-13， IL-1， TNF-α and TIMP-1 in the synovial fluid in knee joints of osteoarthritis patients before and after being treated with Gubi decoction， and to explore the molecular pharmacological mechanisms and clinical efficacy.Methods:Ninety patients with osteoarthritis were recruited in the controlled trial， and randomly divided into Gubi decoction group， Xianling Gubao Capsule group and control group (tablets of glucosamine sulfate). The expression of MMP-13， IL-1， TNF-α and TIMP-1 in the synovial fluid was measured by enzyme-linked immunosorbent assay ( ELISA ) before and after 8 weeks of treatment.Results:The level of MMP-13， IL-1， TNF-α in the synovial fluid decreased significantly after being treated for 8 weeks in Gubi decoction group， Xianling Gubao Capsule group and glucosamine sulfate group (P<0.05). On the contrary，the level of TIMP-1 increased significantly after 8 weeks of treatment. Compared to Xianling Gubao Capsule group and glucosamine sulfate group， the level of MMP-13， IL-1， TNF-α decreased more sharply in Gubi decoction group(P<0.05)， and also the increase of TIMP-1 was significantly greater in Gubi decoction group（P<0.05）.Conclusion:Gubi decoction may play a role in the protection of articular cartilage by decreasing MMP-13， IL-1， TNF-α and increasing TIMP-1 levels in the synovial fluid. The short term effect of Gubi decoction in treatment of osteoarthritis was better than Xianling Gubao Capsule and glucosamine sulfate.