Objective: Present study was designed to investigate effect of gemfibrozil on I/R. Experimental: I/R in rats were induced by bilateral carotid artery occlusion (30 min) and followed by reperfusion (2 hrs). Results and Discussion: Gemfibrozil treated rats demonstrated significant reduction in infarct sizes (P < 0.05) when compared with I/R group of rats, suggested that gemfibrozil markedly attenuated I/R injury. Gemfibrozil treatment demonstrated a significant decreased in malondialdehyde (P < 0.01), and significant increased was observed in level of reduced glutathione (P < 0.01), superoxide dismutase (P < 0.05) and catalase (P < 0.01). Gemfibrozil treatment resulted significant increased in level of Na+-K+ ATPase (P < 0.05) and Mg+2 - ATPase (P < 0.01) and significant reduction of Ca+2 - ATPase (P < 0.01) when compared with I/R group of rats. Conclusion: In conclusion, gemfibrozil attenuated the cerebral ischemia – reperfusion injury and prevention is being shown via membrane stabilization, reducing the oxidative stress, and preventing apoptotic cell death.