[Objective]To investigate the effects of doxycycline on rabbit immobilized osteoarthritis and their mechanism.[Method]Twenty-four rabbits were randomly divided into normal,model,control and treatment groups,with 6 rabbits in each group.All of the animals were immobilized the lower left limbs with plaster bandage for 4 weeks except normal group.Doxycycline was orally given to treatment group.Cartilage degeneration of the medial condyle of femur was observed at 4 weeks and the levels of collagen-Ⅱ,uPA and MMP-13 were tested.[Result]Cartilage degeneration in treatment group was significantly slighter than those in model and control groups.Data of collagen-Ⅱ,uPA and MMP-13 between model and control groups had no significant difference,but a noticeable statistical difference among other groups.The uPA activity was positively correlated with MMP-13.[Conclusion]Doxycycline inhibits the degeneration process of cartilage and improves the structure.The effects may be related to the inhibition of uPA and MMP-13.