Objective:To explore the effect of lamotrigine(LTG) and topiramate(TPM) on the behaviors and electroencephalogram (EEG) of epileptic rats induced by penicillin,and to explore the protection of LTG and TPM for the neurons of hippocampus. Methods:The seizures were observed in the group of epileptic rats induced by penicillin, the group of the rat given LTG, the group of the rat given TPM,the group of the rat given Sodium Valproate, and EEG was recorded in these groups. Immunohistochemical staining was used to observe the expression of Bcl-2 and Bax. Results:The epileptiform discharges decreased in the group of the rat given LTG and the group of the rat given Sodium Valproate, compared the group of the rat given LTG and TPM with the group of the rat given Sodium Valproate. We found that the latencies and durations of seizure between the group of the rat given LTG and the group of the rat given Sodium Valproate had significant difference(P < 0.01). Compared with the epileptic group induced by penicillin,Bcl-2 positive cells increased and Bax positive cells decreased in the group of the rat given LTG and the group of the rat given odium Valproate(P < 0.01). Compared with the group of the rat given Sodium Valproate,Bcl-2 positive cells in the group of the rats given LTG group and in the group of the rats given TPM were increased(P < 0.01). Conclusion:LTG and TPM was better than the Sodium Valproate in the anti-epileptic effects. LTG and TPM can protect hippocampal neuron in the epileptic rats induced by penicillin.