Background and Objective: Copper is one of the main micronutrients of body which plays a key role as a cofactor in the function of metabolic enzymes. Previous studies have shown that copper sulfate (CuSo4) inhibits long-term potentiation (LTP) in slices of hippocampal CA1 region. Whereas LTP is involved in learning and epilepsy, it seems that copper effects on LTP could be associated with its effects on epilepsy and seizure. Therefore, the aim of this study was to evaluate the effect of CuSo4 on seizure induced by pentylenetetrazole (PTZ).Materials and Methods: The effect of various doses of CuSO4 (10, 50 and 100 mg/kg, i.p.), saline (as a control group) or sodium valproate (50, 150 and 100 mg/kg, i.p.) on seizure parameters induced by PTZ (100 mg/kg i.p.) was evaluated in NMRI mice. Twenty minutes after injection of saline or CuSo4, PTZ (100 mg/kg) was injected to induce seizures in animals and seizure parameters were recorded.Results: Comparison of the effect of CuSo4, saline or sodium valproate on seizure parameters such as stage 2 latency, stage 5 latency and stage 5 duration showed that CuSo4 dose-dependently reduced seizure.Conclusion: This study showed that CuSo4significantly inhibits seizure parameters compared with the saline and sodium valproate.