Shock wave lithotripsy (SWL) is commonly used for treatment of renal stones. Free oxygen radicals are involved in the pathophysiology of renal injury due to SWL. We investigated the protective effects of curcumin, which is an antioxidant and nuclear factor kappa-B (NF-kappa B) inhibitor, against renal injury. Forty-eight rats were included and divided into four groups: group 1, control; group 2, SWL (15 kW-1,500 shocks); group 3, SWL + curcumin (curcumin orally 75 mg/kg/day dissolved in 10% ethyl alcohol, 1 day before and 5 days after SWL); and group 4, SWL + vehicle (10% ethyl alcohol). The kidneys were removed on days 7 and 35 after SWL. A sample was fixed in formaldehyde solution. Renal tissues were examined for proximal tubular injury under light microscope. iNOS activity and active subunit of NF-kappa B, p65, were evaluated immunohistochemically using rat monoclonal antibodies interpreting results semiquantitatively. There were significant differences between SWL and control groups on days 7 and 35, considering histological changes under light microscope (P < 0.02). There was a significant decrease in necrosis and fibrosis in the curcumin group as compared to the SWL group. Expressions of iNOS and p65 on days 7 and 35 were at basal levels with immunohistochemical staining. These parameters had high levels in the SWL group (P < 0.02). No significant difference was present between the control and the curcumin groups (P > 0.02). Curcumin, decreasing expressions of iNOS and p65 and serum nitric oxide levels prevented interstitial, glomerular, tubular epithelial and endothelial cellular injuries. We suggest that curcumin, could be used, especially in high-risk patients, as a protective agent to prevent renal injury due to SWL.