Background: Boswellia serrata, have been used traditionally for the management of osteoarthritis (OA) as single extracts, or in other combinations. The aim of the study was to evaluate the safety and efficacy of B. serrata for monosodium iodoacetate (MIA)-induced osteoarthritis using rat animal model. Methods:The B. serrata extract was administered orally once a day for 28 days. To confirm the OA symptoms, the Arthritis Index (AI) was assessed once each week. A histopathological evaluation of the synovial membrane, proteoglycan layer, and cartilage injury was performed. B. serrata extract’s anti-osteoarthritic effects were confirmed by measuring levels of pro-inflammatory mediators/cytokines and matrix metalloproteinases (MMPs) in the serum. Results:After 28 days of treatment, two different doses of B. serrata extract (200mg/kg and 400mg/kg) and Ibuprofen (IB) 20mg/kg were compared with the MIA group.400mg/kg of B. serrata extract significantly reduced the AI score (p<0.001) when compared to IB 20mg/kg. 400mg/kg of B. serrata extract has an equivalent impact on inflammatory cytokine levels of Cyclooxygenase-2 (COX-2), Tumor Necrosis Factor (TNF-α) and MMP-2. 200mg/kg of B. serrata extract has a significant percentage of inhibition of COX-2, TNF-α and MMP-2 in comparison with the standard drug (p<0.001). There was no significant different found in the animal body weight. Conclusion: Overall, our data suggest that B. serrata extract has anti-osteoarthritic effects in MIAinduced OA rats by modulating inflammatory cytokines and MMP-2.