Oxidative damage is involved in the pathogenesis of various nephrotoxicity. In the present study, the protective effect of Vitex agnus-castus leaves was investigated against cisplatin (CIS) induced nephrotoxicity in rats. Thirty  albino male rats were classified into five groups as followed, the first group as control group while the four groups injected with CIS, other were the second group received only CIS, as groups 3, 4 and 5 were administrated 5%, 10%, and 15% Vitex agnus-castus leaves) respectively for 28 days. The results revealed that CIS intoxication impaired kidney function tests. Serum livers of AST, ALTand ALP levels were elevated by CIS administration. Treatment with Vitex agnus-castus at three different levels attenuated these adverse effects and biochemical alterations caused by CIS especially, at the highest level 15%. Nephrotoxicity by CIS resulted in significant elevation of serum triglycerides, total cholesterol, LDL-C, VLDL-C and decreasing in serum HDL-C. Moreover, kidney function tests as serum urea, uric acid and  creatinine were found to be increased and the treatment with Vitex agnus-castus leaves at all treated levels (especially, at the highest level 15%) significantly reversed these adverse alterations. CIS caused significant increased in acetyl cholinesterase (AchE) and significant decreased in total antioxidant and superoxide dismutase activity. Treatment with Vitex agnus-castus has strong radical scavenging activity and antioxidant activity at all level. Therefore, the results of this study show that Vitex agnus-castus leaves can be proposed to protect nephrotoxicity induced by CIS in rats. The results also revealed that the nephrotoxicity effect of Vitex agnus-castus may be attributed to its antioxidant and free radical scavenger effects.