Background: Nanotechnology is a fast growing field that provides for the development of materials that have new dimensions, novel properties, and a broader array of applications. It is now known that the toxic behavior of NPs differ from their bulk counterparts. Even NPs that have the same chemical composition differ in their toxicological properties; the differences in toxicity depend upon size, shape, and surface covering. Hence, before NPs are commercially used it is most important that they be subjected to appropriate toxicity evaluation. Objectives: The aim of the present study was to evaluate the nephrotoxicity induced by CuO and/or Zn-O nano- particles in male rats. Materials and Methods: Twenty adult male rats were grouped randomly into four groups (n=5 each group). Group I (control): Rats were injected with saline intraperitoneally and at a dose of 1.0 ml/kg b.w. for 28 days. Group II (ZnONPs): Rats were administrated orally with ZnONPs (10 mg/kg/day) for 28 days. Group III (CuONPs): Rats were injected with CuONPs (0.5 mg/kg/day, in saline; intraperitoneally) for 28 days. Group IV (ZnONPs + CuONPs): Rats were given orally ZnONPs (10 mg/kg/day) follwed by injected with CuONPs (0.5 mg/kg/day, in saline; intraperitoneally), for 28 days. At the end of the experimental period, rats were anesthetized using light ether. Blood and kidney tissue samples were taken and prepared for biochemical and histological measurements. Results: Serum urea concentration was elevated due treatment of rats with CuONPs, ZnONPs and their mixture compared to control group. Also, CuONPs increased serum uric acid, while ZnONPs reduced serum uric acid and increased creatinine concentration compared to the control group. Treatements of rats with nanoparticls mixture elevated uric acid and creatinine concentration. histopathological abnormalities were observed in kidney of rats treated with CuO-NPs, ZnO-NPs, and CuO-NPs + ZnO-NPs. CuO-NPs, ZnO-NPs, and CuO-NPs + ZnO-NPs –induced histopath