〔Abstract〕 Objective To investigate the effect of resveratrol(Res) on the formation of renal calcium oxalate stone in rats and its relationship with Keap1-Nrf2/HO-1 signaling pathway. Methods Sixty male SD rats were randomly divided into five groups including control group, model group, Res low dose group(L-Res group), Res high dose group(H-Res group) and Res high dose combined with Nrf2 inhibitor ML385 group(H-Res+ML385), with 12 rats in each group. Except for control group, the other groups were given 1% ethylene glycol+2% ammonium chloride to establish kidney stones model for 4 weeks. Meanwhile, the rats were administered with resveratrol or combined with ML385 for 4 weeks. At the end of the experiment, the 24 h urine volume, urine pH, urine Ca2+concentration, uric acid(Ox) content and the serum of urinary nitrogen(BUN), creatinine(Cr) and Ca2+contents were measured in each group. The kidney tissues in each group were obtained and the content of malondialdehyde(MDA) content, activity of superoxide dismutase(SOD) and levels of reactive oxygen species(ROS) in kidney tissues were determined. The formation of calcium oxalate crystals in rat kidney tissue were observed using Von Kossa staining. The proteins expression of nucleus protein Nrf2 and whole proteins Keap1, HO-1 in kidney tissue of rats were detected by Western blot analysis. Results Resveratrol inhibited the formation of calcium oxalate crystals in the kidney tissue of rats, improved the indexes of urine and blood, reduced the levels of ROS and the content of MDA in kidney tissues, increased the activity of SOD, and up-regulated the proteins expression levels of nucleus protein Nrf2 and whole proteins Keap1, HO-1 in kidney tissues. However, combination treatment with Nrf2 inhibitor ML385 significantly inhibit the effects of resveratrol. Conclusion Resveratrol may be inhibit the oxidative damage of kidney tissue by activating Keap1-Nrf2/HO-1 signaling pathway, thereby inhibiting the formation of calcium oxalate crystals in rat kidney tissue, and has the effect of preventing kidney stones.