Despite the fact that past few decades made substantial progress in the understanding of the mechanisms of the liver injury, it has not been possible to design non-hepatotoxic drugs or identify 'very-effective' and 'clinically-safe' antidotes. This is because our comprehension of drug or chemically-induced mechanisms of cell injury and cell death at the molecular level is incomplete. From a mechanistic standpoint, CCL₄-mediated liver injury has emerged as a prominent model. Therefore, this study investigated modulation of a series of key death regulatory genes, such as, Bcl-2, Bcl-xl, Bax, Bad, p53 during the progression of liver injury. Female ICR mice (28-35g) were gavaged with hepatotoxic doses of CCL₄ (1 ml/kg) in corn oil, and sacrificed 0, 6, 12, 18, 24 h later. Blood was collected for serum chemistry analysis and livers for measurement of oxidative stress (MDA, SOD, Nitrate+Nitrite) and western blot analysis. CCL₄-induced massive liver injury was confirmed by increases in ALT activity (U/L in CON: 56±10, 6hr: 195±41, 12hr: 1322±913, 18hr: 20635±1678). Biochemical analysis of the livers reflected corresponding changes in lipid peroxidation, nitric oxide production, genomic DNA fragmentation and SOD activity. Expression of both pro- and anti-apoptotic genes (Bax, Bad, Bcl-2, Bcl-xl) including p53 and Cyt-c were significantly elevated at 18 and 24 hr. Collectively, this study described important changes in the expression of multiple genes during CCL ₄-induced oxidative stress which may potentially play roles during CCL ₄-hepatotoxicity, and extended our understanding of some of the complex interplay between pro- and cell-death regulating genes during the process of liver injury.