Epilepsy is a neurological disease characterized by sudden and synchronized seizures caused by abnormal and excessive electrical discharges in brain neurons. The purpose of this study was to electrophysiologically examine the effects of acute administration of irisin, which is thought to be neuroprotective and increase cell proliferation, at different doses (10 and 100 nM) on the penicillin-induced experimental epilepsy in rats. Fortynine adult male Wistar rats were used in the study. The rats were divided into 7 groups: sham, control group (penicillin), irisin group, the pre-and during-seizure groups of 10 nM and 100 nM irisin. All the substances except penicillin were administered intraperitoneally. The rats were anesthetized using urethane. The bone tissue on the left cerebral cortex was removed and the electrodes were placed in the somatomotor cortex. Thirty minutes before penicillin administration, irisin was administered to the pre-seizure penicillin group at doses of 10 nM and 100 nM. Then, penicillin (500 IU/2 µl) was injected intracortically, and ECoG recording was continued for 120 minutes. On the other hand, 10 nM and 100 nM of irisin were administered to the during-seizure penicillin group after penicillin was injected intracortically and the seizure occurred, and ECoG recording was continued for 120 minutes. The ECoG recordings were analyzed using the PowerLab Chart v.8 software. In conclusion, it was found that irisin prolonged the latency of initial epileptic activity and decreased the number and amplitude of spike-waves in the penicillin-induced experimental epilepsy model. These results suggest that irisin might have an antiepileptic potential.