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Resveratrol, a naturally occurring phytoalexin, acts as an activator of sirtuin 1 (SIRT1) and has been shown to have a neuroprotective role in various models. Healthy adult male Sprague-Dawley rats were subjected to cerebral ischemia in order to study the protective effect of resveratrol on the brain following ischemia, and to investigate the effects of SIRT1 activation on the hippocampus. Untreated and resveratrol-treated rats were anesthetized prior to undergoing surgery to induce middle cerebral artery occlusion followed by reperfusion. SIRT1 expression was evaluated by immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction, and SIRT1 activity was also evaluated. In addition, terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) and Nissl staining assays were conducted and the levels of reactive oxygen species were determined. It was observed that resveratrol significantly decreased the number of TUNEL-positive cells and increased the expression of SIRT1 mRNA in a dose-dependent manner. This was accompanied by increases in SIRT1 protein expression levels and SIRT1 activity. The results demonstrate the neuroprotective and antioxidant effects of resveratrol against ischemia-induced apoptosis in the rat hippocampus.