Abstract: Objective?To investigate the role of extracorporeal shock wave therapy on the protection of cartilage and subchondral bone remodeling in rabbits with osteoarthritis induced by anterior cruciate ligament transaction (ACLT). Methods?Anterior cruciate ligament transaction was performed on 24 adult rabbits to establish knee osteoarthritis models. The rabbits were randomly divided into two groups, with one group receiving extracorporeal shock wave therapy (ESWT) and the other group serving as controls. The ESWT was set at energy 0.16 MPa/time, frequency 5 Hz, 1 200 shock per side, 3 times per week, and a total of 6 times in 4 weeks. Histological observations were undertaken with articular cartilages under mascroscope and microscope; bone mineral density (BMD) was measured. The subchondral bones of femoralcondyle and tibial plateau were given a bone histomorphometry analysis. The levels of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) were detected by ELISA. The expressions of matrix metalloproteinases (MMP-1, MMP-3, MMP-13) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in cartilage were determined by RT-PCR. Results Lower levels?of histological result in medial femoral condyles (by both mascroscope and microscope examinations) and higher levels of BMD (in distal femora) were found in the ESWT treated rabbits compared with the controls (P<0.05). The ESWT treated rabbits also had decreased trabecular bone relative volume and trabecular bone thickness, increased bone separation, lower levels of expressions of MMP-1 and MMP-3, and higher levels of TIMP-1. Conclusion?ESWT can protect cartilage from damages and prevent subchondral sclerosis through regulating MMP-1, MMP-3 and TIMP-1 in cartilages and modulating subchondral bone metabolisms.