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Ischemic brain damage can be explained by the emergence of acute focal or global neurological findings caused by vascular occlusions or hemorrhages. Even in non-fatal cases, stroke is an important pathologic condition with a severe impact on the quality of life, and patients require considerable assistance in the daily lives. The purpose of this study was to investigate the effect of rifampicin on malondialdehyde (MDA) levels and neurological examination of the hippocampal region in rats with transient cerebral ischemia. This experimental study has been performed in a university-affiliated animal lab, Trabzon, Turkey, in 2016. Thirty-eight Sprague Dawley rats weighing 220 - 280 g were used. In this two-vessel occlusion and hypotension ischemia-reperfusion model, the bilateral carotid arteries were temporarily clipped (30 minutes), and blood was withdrawn up to 3 mL of intracardiac volume before the induction of hypotension. After 30 minutes, the clips were removed, and a reperfusion medium was created. One group of 12 rats received intraperitoneal injections of 30 mg/kg of rifampicin every day, and after a 30-minute bilateral carotid artery clipping and hypotension (10 mL/kg). Another group of 12 rats underwent a 30-minute bilateral carotid artery clipping and hypotension (10 mL/kg). The third group consisting of 7 rats underwent skin laceration only. The final group of 7 rats received anesthesia for only 15 minutes. Neurological examinations were performed at the end of days 1, 4, 7, and 10 in all groups. At the end of the 10th day, the animals were euthanized, and their brain tissues were removed. The hippocampi were removed from the brains for biochemical analysis and stored at -76°C in a deep freeze. Ischemic changes in the brain were assessed biochemically by measuring MDA levels in both blood and brain tissue. There was no statistically significant difference between the groups in terms of the mean tissue MDA levels (P = 0.112), but a significant difference was determined in the mean serum MDA values (P = 0.033). Serum MDA values significantly differed between the Group 1 and Group 2 (P = 0.030), but not between Group 1 and Group 3 (P = 0.58). Serum MDA values were also significantly different between Group 2 and Group 3 (P = 0.019), and between Group 2 and Group 4 (P = 0.035). Rifampicin could exhibit a neuroprotective effect on cerebral ischemia-reperfusion injury.