Background: Recent studies have suggested that Mentha longifolia L. extracts (ME) have antioxidant activities. Objective: In this paper, attempts were made to determine the effect of MEin rat stroke model. Methods: Five groups (n=14) were studied the first and second groups (control and sham) received intraperitoneal injection with daily distilled water. The other three groups received 50, 100 and 200 mg/kg/day of the ME for 21 days. Two hours after the last dose, each main group was subdivided into middle cerebral artery occlusion (MCAO) operated for infarct volume assessment and intact subgroup for the assessment of brain and serum antioxidant activity and lipid proxidation of brain and serum, respectively. Results: Pretreatment with ME resulted in a significant reduction in total infarct volume. ME significantly increased antioxidant activity in penumbra and core in comparation with the control. The antioxidant activity of serum in the 100 mg/kg/day group was significantly higher than that of the control group. Malondialdeyde (MDA) level in the penumbra area was significantly elevated in the control group in comparison with other pretreated groups. ME at dose of 100 mg/kg significantly decreased MDA level in core area scale to the control. Moreover, ME with the doses of 100 and 200 mg/kg/day reduced MDA level of serum. Conclusion: ME may protect ischemia/reperfusion induced brain injury by increase in antioxidant activity, decrease in lipid proxidation and reduction in infarction volume.