Erythropoietin (Epo), a cytokine hormone produced in the kidney, promotes the formation of red blood cells in the bone marrow. The penicillin-induced epilepsy model is a commonly used experimental model for epilepsy research. The present study was conducted to elucidate the effect of Epo on penicillin-G (500 IU/2.5 mu l dose, intracortically (i.c)) -induced epileptiform activity in anesthetized adult Wistar-Albino rats (n=39). The animals were randomly divided into four groups as three treatment groups (groups 1-3) and a control group (no drug application). Rats in groups 1, 2 and 3 were intraperitoneally administered 2.000, 4.000 and 6.000 IU Epo/kg, respectively. The effects on penicillin G induced epilepsy were compared across groups using electrocorticography. Epo at 2.000 IU/kg did not cause a significant change (P>0.05) in epileptiform spike-wave activity (number/min) and/or amplitude (mu V) values, whereas the average number of spike-waves per minute and seizure severity decreased significantly in the 4.000 and 6.000 IU/kg Epo groups compared with the control (P<0.05). Consequently, the results of the present study show that administration of Epo has a dose-dependent antiepileptic effect in penicillin induced model of epilepsy in rats.