The objective of this study was to investigate the effects of trimetazidine (TMZ) on tissue damage in kidney after hindlimb ischemia-reperfusion (I/R), by assessing blood biochemical assay and histopathological analysis. Adult male Wistar rats were divided into two groups. TMZ 10 mg kg-1day-1 was administrated twice a day for 10 days to the treatment group (group T, n = 10). Sham group was given only 5% gum arabic (group S, n = 10). On 11th day of treatment, 8 h I/R period was performed on right hindlimb of the rats. At the end of reperfusion period, a 5 ml blood withdrawn from ascending aorta for biochemical assays and their right kidneys were harvested for histopathological examination. Superoxide dismutase, Na+-K+ ATPase, and reduced glutathione levels were significantly increased in group T (P < 0.001). On the other hand, myeloperoxidase and malondialdehyde levels were significantly less in group T than group S (P < 0.001). Kidneys from the sham-operated group displayed intense leukocytic infiltration in histopathological examination. These overall results strongly suggested that TMZ contributes renal protection from hindlimb I/R injury by decreasing systemic oxidative stress. © 2002 Elsevier Science Ltd. All rights reserved.