Objective To explore the influence of tetrahydroxystilbene glucoside (TSG) on the neuron proliferation in epileptic rats and the related mechanisms. Methods 54 healthy SD male rats were randomly divided into three groups: sham-operated group, epilepsy group and epilepsy with TSG treatment group. The epilepsy group was established by stereotactic brain trace injection with kainic acid (KA). TSG solution (3 mg/kg) was injected intraperitoneally at 6 hours after the epilepsy group established, and then q.d. for consecutive 42 days. The sham-operated group and epilepsy group were injected with normal saline. The influence of TSG on cell proliferation of rat hippocampal dentate gyrus BrdU-positive granular cells was observed by immunohistochemistry. Results Compare with the epilepsy group, the amount of glial fibrillary acid protein (GFAP)-positive astrocytes was significantly reduced and dentate gyrus BrdU-positive cells were significantly increased in the TSG group (P<0.01). Conclusions Tetrahydroxystilbene glucoside (TSG) promotes neurogenesis of neural stem cells and neurons, and inhibits the growth of hippocampal dentate gyrus astrocytes in epilepsy rats.