Objective: The purpose of this study was to evaluate the therapeutic effects and mechanism of Qufeng Zhitong (QFZT)capsule for the treatment of osteoarthritis (OA) in a rat model. Methods: 8-10-week-old male Sprague–Dawley rats were randomly divided into the sham group (vehicle-treated), OA group (vehicle-treated), high-dose, middle-dose, low-dose of QFZT capsule-treated groups. OA was induced by transecting the medial collateral ligament and the medial meniscus in the right limb. The Sprague–Dawley rats were treated daily for 12 weeks with different concentrations of QFZT capsule: low (QFZT-L, 128 mg/kg), medium (QFZT-M, 256.5 mg/kg), and high (QFZT-H, 513 mg/kg) by gavage administration for a period of 4 and 12 weeks respectively. Vehicle-treated rats served as controls and administered 0.5% Carboxymethyl Cellulose Sodium (CMC-Na) by gavage on the same schedule. Weekly measurement of dynamic weight-bearing capacity, grip strength, joint swelling was were performed to monitor the progression of disease for 3 weeks. After euthanasia, the knee joints were articular cartilage changes. Pro-inflammatory gene expression in synovial joints was examined to assess the bone and cartilage changes. Gene expression of pro-inflammatory cytokines in synovial joints was measured to determine the therapeutic effect of QFZT. Results: 2 weeks after the treatment, the grip strength and weight-bearing capacity were significantly increased in the QFZT-M and QFZT-H groups, compared with the OA group. The joint widths were decreased significantly in the QFZT-L and QFZT- H groups, compared with the OA group as well. The mRNA level in the articular cartilage of knee joint of IL-1β in the QFZT-L group and IL-6 in the QFZT-H group was significantly suppressed at week 4, compared with the OA group. The radiology score was significantly decreased in the QFZT-H group compared with the OA group 12 weeks after treatment. Furthermore, the rats on QFZT treatment decreased the progression of OA, which was characterised by decreased cartilage degradation. However, the bone changes were no different in OA group and QFZT groups. Conclusion: In a rat model of OA, QFZT capsule shows the tendency to reduce the destruction of cartilage, joint swelling and bone erosion which provides new evidence for the therapeutic potential of QFZT capsule in the treatment of OA in clinics. The translational potential of this article: The QFZT capsule can improve the symptoms of the OA in rodent animal rats by attenuating pain and retarding cartilage damage. This study indicated that the QFZT capsule has the potential clinical application of in OA therapy.