Objective: In this study, we investigated the effect of L-arginine on hemodynamic, biochemical, and histopathological changes in a rabbit model with renal ischemia. Methods: Forty white New Zealand rabbits were used. The rabbits were divided into two groups as the control group (n=20) and L-arginine group (n=20). They were monitored by cannulating the auricular and femoral arteries. An aortic occlusion catheter was inserted through the contralateral femoral artery and was extended to the distal aspect of the left subclavian artery; it was then inflated, and occlusion was performed for 30 min. All rabbits received 4 mL/kg/h of NaCl infusion during the course of occlusion and within the first 60 min of reperfusion. In the L-arginine group, L-arginine was infused at a dosage of 3 mg/kg/h through the auricular vein during the first 60 min of occlusion and perfusion. Blood samples for biochemical parameters [glucose, lactate, hematocrit, blood urea nitrogen (BUN), and serum creatinine] were obtained in the peri-ischemic period, in the 20th minute of reperfusion, and just before sacrificing (48th hour). A histopathological examination was performed in both renal tissues. Histopathological scoring was performed by taking tubular epithelial cell flattening, brush border loss, cytoplasmic vacuolization, cell necrosis, and tubular lumen obstruction into consideration. All animals were sacrificed 48 h after the procedure. Results: A significant difference was found between the L-arginine and control groups in terms of the hemodynamic outcomes and 48th hour BUN and serum creatinine levels (p<0.05). The histopathological examination revealed a mean score of 3.2±0.89 in the control group and 2.60±0.68 in the L-arginine group (p<0.05) (p=0.022). Conclusion: It can be suggested that L-arginine reduces renal ischemia-reperfusion injury and in particular, the histopathological effects. (JAREM 2016; 6: 24-30) [ABSTRACT FROM AUTHOR]