We investigated the neuroprotective effects of Rg(2) in anoxic cultured hippocampal neurons of newborn rats. The cells were divided into a control group, nimodipine group (5 mu mol/L), Rg(2) (0.025 mmol/L), and Rg(2) (0.05 mmol/L) group. The apoptosis rate of hippocampal neurons was measured by flow cytometry with staining of PI. The intracellular calcium ion [Ca2+](i) was observed with fluorospectrophotometer determined by fluorescent probe Fluo-2/AM. The contents of MDA and NO and the activities of SOD in the supernatants of cells were determined by biochemical methods. The results demonstrated that Rg(2) reduced the hypoxia-induced apoptosis, decreased the calcium overload in neurons, increased the activities of SOD, and decreased the contents of MDA and NO in the supernatants of cells. Our study suggests that Rg(2) has a neuroprotective effect against hypoxia-induced neuronal damage in hippocampal neurons mediated by anti-apoptosis, blocking calcium over-influx into neuronal cells, eliminating the free radicals, and increasing the activities of anti-oxidative enzymes to inhibit the oxidative damages caused by anoxic.