Objectives : This study was designed to investigate the effects of Sunbanghwalmyung-eum gamibang on Monosodium iodoacetate-induced osteoarthritis rats. Methods : Forty Sprague-Dawley (SD) rats were divided into 5 groups of 8 rats each. Osteoarthritis (OA) was induced by injecting MIA (2 mg/50 μl) into the joint cavity of the left knee of SD rats belonging to the experimental group, and normal saline was injected into the joint cavity of the left knee instead of MIA in the normal group. To the normal group and the controlled group (OA group), 2 ml of distilled water was orally administered. To the positive control group (Indomethacin group), indomethacin 2 ml at a concentration of 2 mg/kg, to the low concentration group of SHG (Low group), 2 ml of SHG at a concentration of 2 mg/kg, and to the high concentration group of SHG (High group), 2 ml of SHG at a concentration of 4 mg/kg ml was orally administered. The drug was administered for a total of 4 weeks, and histological changes were analyzed by Hematoxylin-Eosin staining and Safranin-O staining. In addition, inflammatory cytokines such as TNF-α, IL-1β, and IL-6, and MMP-13, TIMP-1, and GAGs were immunohistochemically analyzed. Finally, hematological examination, blood biochemical examination, and liver and kidney biopsy were performed. Results : SHG groups (Low and High) inhibited the matrix destruction and damage of the knee joint cartilage in SD rat model, and significantly prevented the reduction in cartilage thickness. In SHG groups, the expressions of TNF-α, IL-1β, IL-6 and MMP-13 were significantly decreased, and the expressions of TIMP-1, GAGs were significantly increased compared with OA group. The safety indicators had no significant differences among five groups. Conclusions : These results show that SHG has cartilage protection capacity, anti-inflammatory effect.