PURPOSE: Resveratrol, extracted from red wine and grapes, has an anti-cancer effect, an antiinflammatory effect, and an antioxidative effect mainly in heart disease and also has neuroprotective effects in the adult animal model. No studies for neuroprotective effects during the neonatal periods have been reported. Therefore, we studied the neuroprotective effect of resveratrol on hypoxic-ischemic brain damage in neonatal rats via anti-apoptosis. METHODS: Embryonic cortical neuronal cell culture of rat brain was performed using pregnant Sprague-Dawley (SD) rats at 18 days of gestation (E1 8) for the in vitro approach. We injured the cells with hypoxia and administered resveratrol (1, 10, and 30 microg/mL) to the cells at 30 minutes before hypoxic insults. In addition, unilateral carotid artery ligation with hypoxia was induced in 7 -day-old neonatal rats for the in vivo approach. We injected resveratrol (30 mg/kg) intraperitoneally into animal models. Real-time PCR and Western blotting were performed to identify the neuroprotective effects of resveratrol through anti-apoptosis. RESULTS: In the in vitro approach of hypoxia, the expression of Bax, caspase-3, and the ratio of Bax/Bcl-2, indicators of the level of apoptosis, were significantly increased in the hypoxia group compared to the normoxia group. In the case of the resveratrol-treated group, expression was significantly decreased compared to the hypoxia group. And the results in the in vivo approach were the same as in the in vitro approach. CONCLUSION: The present study demonstrates that resveratrol plays neuroprotective role in hypoxic-ischemic brain damage during neonatal periods through the mechanism of anti-apoptosis.