Dried leaves from Cedrela sinensis A. Juss. (CS), have been observed to possess various pharmacological activity and contain various antioxidant constituents. The protective effect of ethanol extract of CS on hydrogen peroxide (H2O2)-induced neurotoxicity was examined using primary cultured rat cortical neurons in the present study. Exposure of cultured neurons to 100 μM H2O2 caused a significant neuronal death as assessed by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. The addition of CS, over a concentration range of 10 to 50μg/ml, concentration-dependently prevented the H2O2-induced neuronal apoptotic death. CS (50μg/ml) significantly inhibited H2O2-induced elevation of the cytosolic Ca2+ concentration ([Ca2+]c), which was measured by a fluorescent dye, Fluo-4 AM. CS (30 and 50μg/ml) inhibited glutamate release and generation of reactive oxygen species (ROS) induced by 100μM H2O2. These results suggest that CS may mitigate the H2O2-induced neurotoxiciy by interfering with the increase of [Ca2+]c, and then inhibiting glutamate release and generation of ROS in cultured neurons.