Objective:To investigate the effect of resveratrol on the proliferation and apoptosis of rat renal tubular epithelial cells (NRK-52E) and its possible mechanism. Methods: The NRK-52E cells were cultured in vitro. The NRK-52E cells were divided into four groups: normal glucose (5.6 mmol/L, the NG group), NG plus resveratrol (20 μmol/L, the NG+Res group), high glucose (30 mmol/L, the HG group),and HG plus resveratrol at 20 μmol/L (the HG+Res group). After pretreatment of resveratrol for 6 h and stimulation of HG for 24 h, the rate of cell proliferation was examined by the MTT method, the rate of cell apoptosis was determined by flow cytometry and the expression of GRP78 proteins in the NRK-52E cells was analyzed by Western blot. Results: Compared to the NG group, the rate of cell proliferation and apoptosis in the HG group was increased significantly. Simultaneous incubation with resveratrol inhibited NRK-52E cell proliferation and apoptosis (all P value < 0.01). As compared to the NG group, the expression of NOX4 and GRP78 protein in the HG group was significantly increased (all P value < 0.05). The expression of NOX4 and GRP78 protein in the HG+Res group was significantly decreased than that in the HG group (all P value < 0.05). Conclusion: This data demonstrate that resveratrol may exert antiproliferative and anti-apoptosis effects on rat renal tubular epithelial cells by inhibiting oxidative stress and endoplasmic reticulum stress.