We attempted to elucidate how Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15), a Chinese herbal medicine, attenuates the disruption of hepatic reactive oxygen species metabolism with the progression of carbon tetrachloride (CCl₄)-induced acute liver injury in rats. TJ-15 (100, 250 or 500 mg/kg body weight) was orally administered to rats injected with CCl₄ (1 ml/kg, i.p.) at 6 h after the toxicant treatment. Post-administered TJ-15 reduced progressive liver injury in CCl₄-treated rats at 24 h after the toxicant treatment dose-dependently. The liver of rats treated with CCl₄ alone showed increases in the concentration of thiobarbituric acid-reactive substances, an index of lipid peroxidation, and xanthine oxidase activity and decreases in reduced glutathione and ascorbic acid concentrations and superoxide dismutase, catalase, and glutathione reductase activities at 24 h after the toxicant treatment. The liver of CCl₄-treated rats showed no change in Se-glutathione peroxidase activity and an increase in hepatic glucose-6-phosphate dehydrogenase activity at 24 h after the toxicant treatment. Post-administered TJ-15 attenuated the increases in hepatic thiobarbituric acid-reactive substances and xanthine oxidase activity and the decreases in hepatic reduced glutathione and ascorbic acid concentrations and superoxide dismutase, catalase, and glutathione reductase activities dose-dependently but did not affect the hepatic Se-glutathione peroxidase activity and the increased hepatic glucose-6-phosphate dehydrogenase activity. These results indicate that orally administered TJ-15 attenuates the disruption of hepatic reactive oxygen species metabolism with the progression of CCl₄-induced acute liver injury in rats through its direct and indirect antioxidant actions. The results also suggest that this attenuating effect of TJ-15 could contribute to its preventive effect on the progression of CCl₄-induced acute liver injury.