Adriamycin (ADR) is an anticancer drug used in treatment of a variety of neoplastic lesions. Its use is limited due to diverse toxicities including cardiotoxicity, hepatotoxicity and nephrotoxicity. The present work was conducted to study the effect of fenugreek seed extract on nephrotoxicity induced by ADR in albino rats. Administrating animals with a single dose of ADR (10 mg/kg body weight) induced histopathological, immunohistochemical and biochemical alterations. Kidneys of ADR-treated rats showed many histopathological alterations. The renal tubules were degenerated and the glomeruli were atrophied. The intertubular spaces were infiltrated by inflammatory leucocytic cells. An increase in expression of alfa-SMA was recorded. ADR caused marked elevation in serum creatinine and blood urea nitrogen. Moreover, ADR administration to animals significantly increased the concentration of malondialdehyde and decreased the activity of superoxide dismutase (SOD) in kidney tissues. These changes were time-dependent. Treating animals with ADR and aqueous seed extract of fenugreek (0.4 g/kg) led to an improvement in the histological structure of the kidney together with a decrease in expression of α-SMA. Urea and creatinine were significantly decreased. Moreover, fenugreek treatment reduced the concentration of malondialdehyde (lipid peroxidation marker) and increased the activity of antioxidant enzyme, SOD. In conclusion, the results of the present work indicated that fenugreek seeds had ameliorative effect on kidney damage induced by ADR and this may be mediated by its potent antioxidant effects