BACKGROUND AND OBJECTIVES: Resveratrol (trans-3, 4', 5-trihydroxy-stilbene), a naturally occurring polyphenolic phytoalexin found abundantly in grape skins and red wines, has been reported to protect heart cells from ischemia/reperfusion (I/R) injury through its significant antioxidant properties. Apoptosis of cardiac myocytes is also involved in several cardiovascular diseases, but it remains unknown whether the protective effects of resveratrol in hypoxic myocardial cell injury are mediated via suppression of apoptosis. In this study, we investigated whether resveratrol confers cardioprotection against hypoxia via anti-apoptosis in a hypoxic model of cultured H9c2 cardiomyoblasts. MATERIALS AND METHODS: H9c2 cardiomyoblasts were obtained from the Korean Cell Line Bank. The cultured cells were divided into four groups: a normal control group, a hypoxia group, a group treated with resveratrol (10 microgram/mL) before hypoxic insult, and a group treated with resveratrol (10 microgram/mL) after hypoxic insult. The control group was placed in 5% CO2 incubators, and the hypoxia and resveratrol-treated groups were placed in 1% O2 incubators. Apoptosis was assayed by cytological analysis with Western blotting and real-time PCR for Bcl-2, Bax, and caspase-3. RESULTS: The expression of Bcl-2 was significantly decreased in the hypoxia group compared with the control group, and resveratrol treatment inhibited the hypoxia-induced decline of Bcl-2 in hypoxic myocardial cells. Conversely, the expressions of Bax and caspase-3 were significantly increased in the hypoxia group, while resveratrol inhibited the hypoxia-induced increase of Bax and caspase. In addition, hypoxia significantly increased the ratio of Bax/Bcl-2 expression, but it was significantly decreased in the resveratrol-treated group. CONCLUSION: The present study demonstrates that the cardioprotective effects of resveratrol in hypoxic injury are mediated via the mechanisms of anti-apoptosis.