Carbamazepine (CBZ) and topiramate (TPM) are among commonly used antiepileptic drugs. The acute actions of these drugs are well known but the effects of long-term use on partially induced epileptiform characteristics are yet to be clarified. The rats were received CBZ (154 mg/kg/day), TPM (10 mg/kg/day) or tap water by gavage. We investigated penicillin-induced cortical epileptiform activity and electroencephalogram spectral power of rats by using electrocorticogram recordings. Animals were anesthetized with i.p. urethane (1.25 g/kg). Analysis of electroencephalogram recordings prior to epileptiform activity revealed that 3-week treatment of CBZ significantly increased relative power of delta (P < 0.01) while reduced alpha (P < 0.017) and beta (P < 0.017) relative power compared to both control group and TPM group. TPM had no effect on absolute power and relative power of any frequency band. TPM treatment of 21 days significantly reduced the spike frequency (P < 0.01). This preventive effect was missing in CBZ-treated rats. Upon the application of the last dose of drugs during ongoing epileptiform activity, the drugs suppressed the epileptiform activity. However, TPM was more rapid and effective than CBZ. In conclusion, our in vivo electrophysiological data suggest that TPM is more effective in animal model of partial epilepsy at the applied doses in this study.