Free radicals and selenium (Se) deficiency are involved in pathogenesis of epilepsy. Topiramate (TPM), a new anticonvulsant, was reported to possess neuroprotective effect via inhibition of free radicals. We investigated the effects of Se and TPM on pentylentetrazol (PTZ)-induced blood toxicity in rats. Forty male Wistar rats were equally divided into five groups. First and second groups were used as control and PTZ group, respectively. TPM and Se were administrated to rats constituting third and forth groups for 7 days, respectively. The TPM and Se combination were given to animals in fifth group for 7 days. At the end of 7 days all groups except the first group received single dose PTZ. The brain cortex samples were taken at 3 h of PTZ administration. PTZ resulted in significant increase in plasma and erythrocytes lipid peroxidation (LP) levels although plasma vitamin E concentrations and erythrocytes glutathione peroxidase (GSH-Px) activities were reduced by PTZ. The plasma and erythrocytes LP levels in third, fourth, and fifth groups were decreased as compared to second group although GSH-Px and reduced glutathione values increased in the groups. Vitamin C and E concentrations were increased through fourth and fifth group only. Vitamin A concentrations were not changed by PTZ. In conclusion, Se and TPM seem to have protective effects on the PTZ-induced blood toxicity by inhibiting free radical supporting antioxidant redox system.