Ischemia-reperfusion (I-R) injury remains the leading cause of acute renal failure. The purpose of this experimental study was to determine the role of dexmedetomidine on histologic alterations induced by renal I-R in rats. In the present study, thirty male Sprague-Dawley rats weighing 200-220 g were randomly assigned into three groups: the sham-control group (group 1, n = 10), the R/untreated group (group 2, n = 10), and the I-R/dexmedetomidine-treated group (group 3, n = 10). For group one, we performed a sham operation. The abdomen was dissected, the right kidney was harvested, and then the left renal pedicle exposed. Renal clamping was not applied. For group 2, rats underwent left renal ischemia for 60 minutes followed by reperfusion for 45 minutes. For group 3, the same surgical procedure as in group 2 was performed, and dexmedetomidine (100 microg/kg, intraperitoneal) was administrated at the starting time of reperfusion. The rats were sacrificed after reperfusion, and the kidney tissue was harvested. The histopathological score in the kidney of the I-R/dexmedetomidine-treated group rats was significantly lower than that of I-R/untreated group rats. This score in I-R/untreated group rats was higher than the other two groups, which was statistically significant. In the I-R/untreated group rats, kidneys of untreated ischemia rats showed tubular cell swelling, cellular vacuolization, pyknotic nuclei, medullary congestion, and moderate to severe necrosis. Treatment with dexmedetomidine shows normal glomeruli and slight edema of the tubular cells. These findings provide the first evidence that dexmedetomidine can reduce the renal injury caused by I-R of the kidney, and may be useful in enhancing the tolerance of the kidney against renal injury.