Background: Impaired wound healing, which is due to various external and internal factors that are involved in wound pathophysiology, leads to high rates of morbidity and mortality worldwide. Oxidative stress injury is an important factor that affects wound healing by changing the whole healing process. So, resveratrol, a dietary fruits polyphenol, which is known for its antioxidant properties, maybe the candidate to accelerate the wound-healing process. Methods: The Human Umbilical Vein Endothelial Cells (HUVECs) was used for in vitro experiments to evaluate the effect of resveratrol on hyperglycemia-induced gene expression, oxidative stress and cell proliferation. The diabetic rat model was used to evaluate the effect of resveratrol on cutaneous burn injury healing process. Results: Increases in H2O2 decreased cell viability with the 0-800 mM concentration range, and resveratrol could protect HUVECs against H2O2-induced injury. The scratched wound closed rate in H2O2 group was significantly smaller than the Control group (p < 0.05) and Resveratrol + H2O2 group (p < 0.05). The fluorescence intensity of ROS was lower in Control and Resveratrol + H2O2 groups than H2O2 group. Correspondingly, compared to H2O2 group, the expressions of Mn-SOD and nuclear Nrf2 (N-Nrf2) was up-regulated in Resveratrol + H2O2 group (p < 0.05). In vivo, compared with the saline group, using resveratrol could significantly accelerate wound healing of rats on Day 14 (p < 0.05) and make the regenerated skin structure more complete and inflammatory response lower. Moreover, the expressions of Mn-SOD was significantly up-regulated after using resveratrol. Conclusions: Resveratrol has the positive effects on promoting the acceleration and quality of skin wound healing, which maybe at least in part caused by the up-regulation of nuclear Nrf2 and Mn-SOD that subsequently attenuated oxidative stress. (c) 2020 Published by Elsevier Ltd.