Objective To discuss the protective effects of Ginsenoside (Gin) against Glutamic acid (Glu) excitotoxicity in hippocampal neurons. Methods By using the model of Glu excitotoxicity on primary cultured hippocampal neurons and the method of measuring [Ca 2+ ]i in neurons by means of Fura-2 fluorometry, we studied the protective effects and mechanism of Gin against the excitotoxicity. Results Gin could reduce the level of LDH leaked from cultured neurons by Glu excitotoxicity( P 0.01) and selectively inhibit the increasing of [Ca 2+ ]i induced by high level Glu( P 0.01). Conclusion The neuro-protective activities of Gin against excitotoxicity were mediated by reducing [Ca 2+ ]i in neuronal cells.