Sodium arsenite (NaAsO2) is a well-established environmental carcinogen that has been found to cause various human malignant tumors. Thus, how to prevent the deleterious effects caused by NaAsO2 has received widely concerns. Resveratrol (3,4',5-trihydroxystilbene), a polyphenol found in numerous plant species, has recently been known as a natural and powerful antioxidant. However, whether resveratrol could attenuate the toxicity of NaAsO2 and its detailed mechanisms have not been reported. In this study, the protective effects of resveratrol against NaAsO2-induced oxidative and genetic damage as well as apoptosis were evaluated for the first time. We demonstrated that cotreatment of human bronchial epithelial cell with 5 μM resveratrol for 24 h effectively reduced the levels of 30 μM NaAsO2-induced reactive oxygen species, chromosomal and DNA damage, and cell apoptosis. Revseratrol was also showed to significantly elevate the concentration of glutathione (GSH) and the activities of its relevant enzymes as compared with NaAsO2 alone, indicating that resveratrol ameliorates the toxicity of NaAsO2 by modulating the process of GSH biosynthesis, recycling and utilization. Our findings further suggest that GSH homeostasis represents one of the detoxification mechanisms responding to NaAsO2 exposure, and resveratrol plays a protective role in the regulation of oxidative and genetic damage as well as apoptosis through the modulation of GSH homeostasis.