Temporal lobe epilepsy (TLE) is a long lasting neurological disorder in which patients suffer from spontaneous seizures. New treatments with novel mechanisms of action are needed to help those patients whose seizures are resistant to available drugs. In this study, we investigated the possible neuroprotective effect of berberine in an intrahippocampal kainate model of TLE in rat. In the present study, the anticonvulsant and antioxidant effects of intraperitoneal administration of berberine (25, 50 and 100 mg/kg), was evaluated in intrahippocampal kainate (4µg)-induced TLE in rats. The results showed that the kainate rats exhibit acute and spontaneous seizures in 24 hours and two weeks after intrahippocampal kainic acid injection. Administration of berberine, significantly decreased the Racine score and rate of incidence of seizure in kainate rats (P<0.05). On the other hand, berberine ameliorated the lipid peroxidation (P<0.001) and nitrite (P<0.001) level, but had no effect on SOD activity. These data suggest that berberine pretreatment could attenuate spontaneous recurrent seizures. Since, administration of berberine decreased lipid peroxidation in kainate rats, it seems that berberine favorable effect is due to its effectiveness in lessening of oxidative stress in rat.