Depleted uranium (DU) is a major health hazard environmental pollutant that is used primarily in military activity. Considerable evidence suggests the imuno-, geno- and reproductive toxicity of uranyl acetate (UA), a soluble salt of DU. A broad spectrum of data in literature indicates the antioxidant, antiapoptotic and cytoprotective properties of thymoquinone (TQ) and N-acetylcysteine (NAC). Therefore, we examined the ability of the two antioxidants, TQ or NAC to ameliorate UA hepatotoxicity in adult Wistar rats. The rats were injected intraperitoneally with a single dose of uranium as uranyl acetate (UA) (1 mg/kg body weight) alone or in combination with subsequent supplementation with NAC or TQ for 25 days. The obtained results showed that NAC or TQ administration in UA intoxicated rats ameliorated the adverse changes in the liver biochemical indices and hepatocellular features. They decreased alanine amino-transferase and aspartate amino-transferase; icreased glutathione and nitric oxide levels and the activities of superoxide dismutase and catalase, however, they decreased lipid peroxides and carbonyl protein content compared with UA group. In addition, the present data indicated that TQ provided stronger protection against UA induced hepatotoxicity than NAC.