Background:L-Arginine (L-arg) and Prostaglandin E<sub>1</sub> (PGE<sub>1</sub>) have been used effectively as single agents to ameliorate renal ischemia-reperfusion injury. We hypothesized that combined treatment with L-arg and PGE<sub>1 </sub>would be more effective. Materials and Methods: The left renal artery of male Sprague-Dawley rats was clamped for 45 min and the right kidney was removed. Fifty six rats were randomly allocated into 5 groups each consisted of 12 rats except sham group (n = 8). (1) sham, underwent right nephrectomy only; (2) control, untreated ischemic rats; (3) L-arg group, L-arg-treated ischemic rats; (4) PGE<sub>1</sub> group, PGE<sub>1</sub>-treated ischemic rats; (5) L-arg+PGE<sub>1</sub> group, ischemic rats treated with both L-arg and PGE<sub>1</sub>. Renal function and histology were assessed on days 2 and 7 postoperatively. Results: All rats, except control ones, showed a significant improvement of renal function towards normal on postoperative day 7. Serum creatinine and creatinine clearance were significantly better in L-arg+PGE<sub>1</sub> group compared to all other groups on day 7. With the exception of sham-operated and L-arg+PGE<sub>1</sub>-treated animals, all other groups showed significant increases in fractional excretion of sodium (FE<sub>Na</sub>) in response to renal ischemia-reperfusion. The severest tubular damage was determined in the kidneys of control rats. Rats treated with L-arg+PGE<sub>1</sub> had the least severe tubular damage. Conclusion: The administration of either L-arg or PGE<sub>1</sub> attenuates both functional and structural consequences of renal warm ischemia. A near total protection might be achieved when both agents are administered concomitantly.