Zinc oxide nanoparticles (ZnO NPs) are produced in high tonnage each year; they are widely used in consumer and industrial products, also now finding applications in bioimaging and drug delivery. In the present study, comparison between ZnO NPs (39 nm) and its bulk/micron form (particle size = 5 µm) on liver function of rats was determined. In our study, liver enzymes biomarkers, serum lipid profile, zinc concentration, and histopathological examination in liver tissues were used to evaluate liver injury. Moreover, lipid peroxidation (malondialdehyde), nitric oxide, and reduced glutathione levels were determined to detect the oxidation–reduction process in liver tissue. The results showed dose-dependent toxicity of ZnO NPs. Three different dose levels (25, 50, and 100 mg/kg bw) were used, and the 100-mg/kg bw ZnO NPs group showed the most significant changes in liver enzymes and histopathological structure, as well as redox state. The dose of 100 mg/kg bw of ZnO bulk group showed no significant effects on liver function. The study concluded that ZnO NPs caused hepatic impairments.