Carbon tetrachloride (CCl₄) is commonly used as a chemical inducer of experimental liver injury. In addition, many studies showed that CCl₄ can induce kidney damage. In the current study, we evaluated the protective effect of zinc (Zn) against CCl₄-induced nephrotoxicity. We hypothesized that this protective effect would result from the ability of Zn to serve as an inducer of metallothionein (MT), a known endogenous scavenger of free radicals. We administered Zn (as ZnSO₄) 50 mg/kg subcutaneously once daily for 3 successive days prior to a single intraperitoneal administration of CCl₄ 4 g/kg in male ddY mice. Our results showed that Zn pretreatment significantly decreased creatinine and blood urea nitrogen levels and reduced renal histopathological damage at 6 h post-CCl₄ injection, observations consistent with enhanced antioxidative activity in the kidney. Moreover, kidney MT levels in the Zn+CCl₄-treated group decreased by greater than 70% compared with levels in the Zn-alone group, implying that MT was consumed by CCl₄-induced radicals. These findings suggest that prophylaxis with Zn protects mice from CCl₄-induced acute nephrotoxicity, presumably by induction of MT, which in turn scavenges radicals induced by CCl₄ exposure.