Arsenic has been reported to cause damaging effects on different body organs. This study was designed to evaluate the protective effect of resveratrol (RSV) against arsenic trioxide (ATO)-induced intoxication in experimental animals. Twenty-four Wistar rats were allocated in 4 groups: group 1: control group, received normal diet; group 2: received ATO (3 mg/kg); group 3: received RSV (8 mg/kg) 30 minutes before administration of ATO; and group 4: received ascorbic acid (25 mg/kg) 30 minutes before administration of ATO. Treatments were given to experimental rats daily for consecutive 8 days. At the end of experimental period, bioaccumulation of arsenic in liver and kidney was assessed by hydride generation-atomic absorption spectrophotometer to investigate the association of arsenic accumulation with histological aberrations. Following parameters were also investigated: serum biochemical profile (alanine aminotransferase, aspartate transaminase, alkaline phosphatase, blood urea nitrogen, and creatinine) for evaluation of liver and kidney functions and lipid peroxidation and oxidative stress (malondialdehyde, glutathione, superoxide dismutase, catalase, and glutathione peroxidase) in tissue homogenates of liver and kidney for estimation of oxidative status. The findings of this study indicate that RSV remarkably ameliorated the hepatic and renal toxicity in arsenic-exposed rat model due to its strong antioxidant potential.