Corticosteroids are extensively used in treatment of many diseases. In neurosurgery practice, dexamethasone (DEX) is commonly used particularly in cerebral edema secondary to brain tumors, head trauma, and central nervous system infections. There are some uncertainties surrounding the secure use of DEX in patients with epilepsy or seizures induced by diseases of the central nervous system such as head trauma and brain tumors. Despite its extensive use, the effect of DEX on epileptiform activity is unclear. In this study the effect of DEX on epileptiform activity was investigated in rats. The effects of 1, 3, and 10 mg/kg DEX on epileptiform activity was compared with effects of antiepileptic drugs commonly employed in treatment of epilepsy, namely phenytoin (PHT) 50 mg/kg and levetiracetam (LEV) 50 mg/kg that were administered intraperitoneally for 1 week. All groups were administered intracortical penicillin (500 IU) to induce epileptiform activity. DEX at the doses of 3 mg/kg and 10 mg/kg significantly reduced spike frequencies compared to the initial values. In conclusion, we think that DEX can effectively decrease the epileptiform activity. (C) 2014 Elsevier B.V. All rights reserved.