Abstract: Zinc oxide nanoparticles (ZnO-NPs) are used in many industries and medications, increasing the exposure to ZnO-NPs that may have harmful side effects. So, we studied the hepatotoxic effect of ZnO-NPs and explored the role of vitamin E in the reduction of their toxic effects. Forty male albino rats, divided into four groups (10 rats per group) were included in the study; control group, ZnO-NPs intoxicated group, vitamin E control group and vitamin E protected ZnO-NPs intoxicated group. ZnO-NPs were given in a dose of 400 mg / kg body weight for seven days. Vitamin E was given in a dose of 100 mg / kg body weight for four weeks. Our results showed that ZnO-NPs induced liver damage indicated by significant increase of serum ALT and AST and significant decrease of serum albumin and total protein levels. Moreover, ZnO-NPs induced oxidative stress in the liver suggested by significant elevation of malondialdehyde level and significant reduction of reduced glutathione level, glutathione peroxidase activity and glutathione peroxidase-1 expression in liver homogenate. Furthermore, ZnO-NPs caused significant increase in the serum pro-inflammatory biomarker, tumor necrosis factor alpha (TNF- α). On the other hand, vitamin E alleviated the liver damage, oxidative stress and the elevated serum TNF- α induced by ZnO-NPs