Background: Magnesium (Mg2+) is the second most abundant cation (after potassium) in the cell and plays an important role in various biological functions, including cell cycle, channel regulation, ATPase activity, metabolic regulation, etc. Magnesium deficiency increased incidence of cardiovascular diseases, including hypertension, stroke, and atherosclerosis as well as gastrointestinal disorders, such as loss of appetite, nausea, and vomiting. Considering the antioxidant activity of magnesium and the role of oxidative stress in the pathophysiology of epileptic seizures, the present study was conducted to investigate the effect of magnesium sulfate on pentylenetetrazole (PTZ) -induced seizures in adult male Wistar rats.Methods: In the present experimental study, the rats were randomly divided into eight groups: normal control, magnesium sulfate (0.05, 0.1, and 0.2 g/kg intragastrically, daily) alone, seizuric control rats (PTZ, 35 mg/ kg, i.p.), magnesium sulfate (0.05, 0.1, and 0.2 g/kg intragastrically, daily) together with PTZ, and treatment was performed accordingly. Administration of magnesium sulfate (0.05, 0.1 and 0.2 g/kg) was launched 1.5 h before the first dose of PTZ and continued up to 28 days. The rats were sacrificed on day 29 and parameters of oxidative stress, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and malondialdehyde (MDA) activity were measured in liver homogenate. Data were evaluated running oneway analysis of variance.Results: Administration of magnesium sulfate (0.1 and 0.2 g/kg) significantly increased the levels of antioxidant enzymes, including SOD, CAT, GPX, while it decreased MDA levels (p<0.05).Conclusion: It seems that presumably magnesium sulfate is effective in providing protection against oxidative stress induced by PTZ.