Urinary N-acetyl-β-D-glucosalninidase (NAG) has been proved to be a useful marker of early renal injury as a result of factors such as lead toxicity. In this study the effect of lead acetate on the kidney and its correlation with the nitric oxide (NO) system was investigated by determining the NAG release in perfused kidney of rat. Lead acetate caused a time- and dose-dependent increase in enzymuria. The effect of concurrent perfusion with lead and arginine (L-Arg) or L-NG-nitro arginine methyl ester (L- NAME) (precursor of NO and inhibitor of NO synthase respectively) in the perfusion fluid was also studied by measuring NAG activity in the perfusate of rat kidney. L-Arg (2 mM) decreased (p<0.001) and L-NAME (0.1 mM) increased significantly the lead-induced enzyme release from the kidney in a time-dependent manner. Moreover, histological studies by light microscope showed that some of the epithelial cells in the proximal convoluted tubules are degenerated or necrotic and desquamated into the lumens in rats treated with lead acetate. This change occurs at a concentration of 50 µg/dl for lead acetate and is increased in the presence of L-NAME. However, an addition of L-Arg had no effect on histological indicators of lead nephrotoxicity. This may suggest that lead may interfere with the NO system in the kidney of rat.