Introduction: Iron overload has been implicated as an important factor for nephropathy by hydroxyl radicals production. On the other hand nitric oxide (NO) asa reactive free radical, has numerous effects on kidney. However at high concentration it has been suggested to have toxic effects. In this study the interaction between iron overload and NO system on renal function were evaluated in rats. Materials & Methods: Iron dextran (Fe), L-arginine (L-arg, precursor of NO), and L-NAME (in hibitor of NO production) were used. Serum concentration of creatinine was measured as an index of renal injury. Animals were divided in to five groups as follows: Sham (recieving normal saline intraperitoneally, ip); Fe (600 mg/kg ip); L-arg (400 mg/kg ip in divided doses); Fe+L-arg; and Fe+L-NAME (L-NAME with a dose of 80 mg/kg ip in divided doses). Twenty hours after injections serum concentrations of creatinine were determined. Results: After ANOVA and post test of Newman Keul's, the following results were obtained. Creatinine concentrations were significantly higher in Fe group compared toL-arg and Sham groups (P<0.05). In Fe+L-NAME group the value was significantly higher than Sham and L-arg and Fe+l-arg groups (P<0.01) while in Fe+L-arg group was lower than Fe group. However, it wasn't significantly different from L-arg and Sham groups. Conclusion: This study suggests that a protective role for NO in Fe loaded rat kidney.