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. Various scientific groups are keen about this technology and are devoting themselves to the development of more, new, and better nanomaterials. In the near future, expectations are that no field will be left untouched by the magical benefits available through application of nanotechnology. Objectives: The aim of the present study was to evaluate the hepatic toxicity induced by nano-CuO and Zn-O mixture 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 (10mg/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 (10mg/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 liver tissue samples were taken and prepared for biochemical and histological measurements. Results: Serum total protein, albumin, and globulin concentrations in rats treated with CuONPs, ZnONPs and their mixture were significantly lower compared to the control group. On the other hand, significant increase in total bilirubin levels in rats treated with CuONPs, ZnONPs and their mixture treated groups compared to the control group. Pronounced increase in total bilirubin due treatments of rats with nanoparticles mixture compared to the individual treatemnts of each nanoparticles tested. The ALT, AST and AlP values in the CuONPs rats group were significantly higher compared to the control group.