Resveratrol is a non‑flavonoid polyphenol compound with a stilbene structure. As a type of phytoalexin produced under stress in plants, it improves the plant's resistance against pathogens and environment deterioration, and performs important functions beneficial to human health, such as anti‑cancer, anti‑oxidation, regulating blood lipid levels and prolonging life span. The effects of resveratrol were examined in a rat model of osteoarthritis (OA) and observed to ameliorate inflammatory damage and protect against OA. In the present study, resveratrol significantly inhibited the induction of clinical scores in rats with OA. Resveratrol inhibited tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6 and IL‑18 expression levels, and decreased caspase‑3/9 activity in rats with OA. Inducible nitric oxide synthase, nuclear factor (NF)‑κB, phosphorylated‑(p)‑AMP‑activated protein kinase and sirtuin 1 protein expression were significantly suppressed and heme oxygenase 1 (HO‑1) and nuclear factor erythroid 2‑related factor 2 (Nrf‑2) protein expression was stimulated in rats with OA treated with resveratrol. The current results indicate that resveratrol ameliorates inflammatory damage and protects against OA in a rat model of OA via NF‑κB and HO‑1/Nrf‑2 signaling.