Resveratrol (Res) has been reported to inhibit tumor initiation, promotion, and progression in a variety of cell culture systems depending on the specific cell type and cellular environment. In the present study, we determined the effect of Res on the cell growth and apoptosis of rat glioma C6 cell line as well as mouse fibroblast 3T3 cell line, in vitro. Concurrently, we investigated whether caspase-3 is involved in the Res-induced apoptosis of rat glioma cells. Exposure to Res exhibits a significant anti-proliferative effect and induces an increase in the population of apoptotic cells on C6 cells in a concentration- and time-dependent manner, but not for normal 3T3 fibroblast cells, as measured by methyl thiazolyl tetrazolium assay and flow cytometer. Distinguished increase of C6 cells in S phase is observed after the treatment of Res as compared to insignificant change in cell cycle distribution of 3T3 cells. TdT-mediated dUTP nick end labeling fluorescence staining, HE staining, and scanning electron microscope revealed abnormal morphology and ultrastructure in C6 cells treated with Res. Our data showed that Res can increase the expression and induced the activation of caspase-3 in rat glioma C6 cells. These results suggest that Res has significant apoptosis-inducing effect on C6 glioma cells other than normal fibroblast 3T3 cells in vitro and caspase-3 may act as a potential mediator in the process.