The purpose of this study is to determine the effects of doxorubcin and nanoparticle Zinc oxide in normal and hepatotoxicity induced by Carbon tetrachloride(CCl4 ) in rats. The nanoparticle of ZnO (ZnO-NPs) were prepared by wet reaction of Zn acetate and sodium hydroxide. The prepared ZnO NPs were identified and characterized by Scanning Electron Microscope (SEM) with Energy Dispersire X-ray spectrometer ( EDX ) Fourier Transmitter Infra Red ( FTIR ) and UV visible , the structure of particles was 100 nm. The investigated parameters were Liver enzymes, Protein electrophoresis and DNA gel electrophoresis in normal and injected rats by CCl4. Atotal of forty eight adult male albino rats (130-165 g) were divided into 8 groups, each of 6 rats. Group one was kept as a control –ve, second and third groups were injected intraperitoneally with DOX(6mg/kgb.wt) and nZnO(5mg/kgb.wt) respectively for 3 successive days. While fourth group was injected intraperitoneally nZnO followed by DOX for the same period. On the other hand, other four groups were injected subcutaneously with CCL4 50% (0.1 ml/100g.b.wt.twice/week for two weeks )to induce DNA damge and hepatotoxicity. One of this groups was kept as a control +ve (CCL4 groups). Sexth and seventh groups were injected intraperitoneally with DOX (6 mg/kgb.wt) and nZnO (5 mg/kgb.wt) respectively for the same period. While eighth group was injected intraperitoneally nZnO followed by DOX for the same period. At the end of experimental period, blood samples were collected from each rat for biochemical analysis and the rats were sacrificed to illustrate DNA damage in hepatocytes. Subcutaneous injection of CCL4 caused significant increase in serum levels of aspartateaminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphate (ALP) while the levels of malondialdhyde (MDA), Total Antioxidant Capacity (TAC), albumin and globulin were significantly decreased .The smear on agarose gel had been observed in CCL4 injected groups indicating random DNA fragmentation. Rats were injected DOX showed similar changes. NZnO significantly restored the serum levels of the biochemical parameters and DNA damage directed toward to normal as compared with the control +ve group (injected with CCl4). Thus, it can be concluded that zinc oxide nanoparticles followed doxorubicin intraperitoneally injection improved the alteration of some serum biochemical parameters and DNA damge induced by CCL4.