Abstract. The aim of the present study was to determine the protective effects of resveratrol on a rat model of osteoporosis and examine the associated mechanisms of its action. Rats were randomized into the following groups: Control, osteoporosis, osteoporosis + low-dose resveratrol, osteoporosis + middle-dose resveratrol and osteoporosis + high-dose resveratrol groups. Resveratrol treatment was administered 7 days after surgery for 8 weeks. ELISA assay was used to analyze alkaline phosphatase (ALP) and osteocalcin (OC) protein levels. Western blotting was performed to assess the protein expression of sirtuin 1 (SIRT1), nuclear factor (NF)-κB and NF-κB inhibitor (IkB) α. In the present study, the results indicated that resveratrol markedly improved the bone mineral density value, femoral porosity and bone mechanical tests in osteoporosis rats. Administration of resveratrol significantly decreased the serum levels of ALP and OC in rats with osteoporosis. Finally, treatment with resveratrol significantly promoted the protein expression of SIRT1, suppressed NF-κB and activated the IkBα protein expression in rats with osteoporosis. In conclusion, treatment with resveratrol significantly improved the final body weight of the osteoporosis rats via the SIRT1-NF-κB signaling pathway. The present study suggested that resveratrol exerted a protective effect on osteoporosis through activation of the SIRT1-NF-κB signaling pathway in rats.