Background: After reestablishment of blood flow to ischemic limb recirculation of free radicals may cause ischemia-reperfusion injury in many organs. This study designed to investigate effects of hydrocortisone and alprostadil distant injury to kidneys by both measuring biochemical markers of oxidative stress and histopathologic examination in an experimental rat model of hind limb ischemia-reperfusion. Materials and Methods: This study conducted in Isfahan University of Medical Sciences during 2011-2012. Ischemia was established by infra renal aortic clamping for 60 min in 32 male Wistar rats. Animals were divided into those receiving alprostadil (group ischemia-reperfusion plus alprostadil (IR/A), n = 8), those receiving hydrocortisone (group ischemia-reperfusion plus hydrocortisone (IR/H), n = 8), control group (group ischemia-reperfusion (IR), n = 8), and sham group (n = 8). After 120 min of reperfusion both kidneys were removed. Levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) as indirect markers of oxidative injury was measured. Finally all data in different groups were compared using the analysis of variance (ANOVA) test by Statistical Package for Social Sciences (SPSS) version 16. Results: Administration of alprostadil or hydrocortisone does not improve the biochemical parameters of oxidative injury including MDA and SOD. However, statistically significant difference was seen in GSH level among sham and IR groups. Mean (΁ standard deviation (SD)) concentration of GSH in IR, IR/A, IR/H, and sham groups were 1028.77 (72.65), 924.82 (70.66), 1000.28 (108.77), and 846.69 (163.52), respectively (P = 0.015). Histopathological study of specimens did not show any significant changes between groups. Conclusion: Alprostadil and hydrocortisone do not improve the kidney GSH, SOD, and MDA level and kidney releases its GSH reserve during ischemia-reperfusion event, and another point is that, 3 h of ischemia-reperfusion does not develop injury in kidney.