(-)-Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea. Many health promoting effects of EGCG have been reported based on its antioxidative and gene modulation properties, but no study has demonstrated a protective effect of EGCG against glutamate-induced neuronal damage. Excessive glutamate stimulation on neuronal cells leads to accumulation of reactive oxygen species (ROS) which ultimately contribute to cell death in stroke, trauma and other neurodegenerative disorders. In this study, mouse hippocampal cell line, HT-22, was used to determine the effect of EGCG on glutamate neurotoxicity. It was found that EGCG protected HT-22 cells against glutamate neurotoxicity when administered 10 h after glutamate incubation. The protective action of EGCG is mainly due to its antioxidative effect.