Objective: Sepsis can cause serious acute kidney injury inbacterium infected patients, especially for intensive care patients. Icariin is a bioactive flavonoid, which has renal protection and anti-inflammation effects. This study investigated the mechanism underlying the attenuation of Lipopolysaccharide (LPS) induced renal injury by icariin. Methods: ICRmice were treated with LPS (25 mg/kg) with or without treatment with icariin (20 or 40 mg/kg for three days). Renal function, histological changes, degree of oxidative stress and tubular apoptosis were examined. The effects of icariinon LPS-induced expression of renal TNF-alpha, NF-kappa B, MCP-1, ICAM-1, cleaved caspase-3 and Bcl-2 family proteins were evaluated. Results: Treatment of mice with LPS resulted in renal damage, showing an increase in blood urea nitrogen and creatinine levels, tubular damage, oxidative stress and apoptosis. These renal changes could be significantly improved by icariin treatment, both at two dosages. Examination of cytokines, chemokines and molecular mediators involving in inflammation and apoptosis of the kidney revealed that treatment of LPS increased levels of TNF-alpha, NF-kappa B, IL-1 beta, cleaved caspase-3, MCP-1, ICAM-1 and decreased the level of BCL-2. All these disturbed expressions were reversed by treatment with icariin. Conclusions: These results indicate that icariin ameliorates the LPS-mediated nephrotoxicity via improving renal oxidant status, consequent NF-kappa B activation and inflammation cascade and apoptosis, and the following disturbed expression of apoptosis related proteins.