Baicalin (BA) is a flavonoid compound purified from Scutellaria baicalensis Georgi that is used as a traditional Chinese herbal medicine. Baicalin was studied for the mechanism of its inhibitory effects on the tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity and lipid peroxidation in rat liver system. Baicalin expressed an antioxidant property by its capacity for quenching the free radicals of 1,1-diphenyl-2-picrylhydrazyl (DPPH). Further investigations using the t-BHP-induced cytotoxicity in rat primary hepatocytes demonstrated that baicalin, at the concentrations of 2-220 microM, significantly decreased the leakages of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT), and the formation of malondialdehyde (MDA) induced by 30 min treatment of t-BHP(1.5 mM). Baicalin also attenuated the t-BHP-induced depletion of glutathione (GSH) and high level of DNA repaired synthesis. An in vivo study in rats showed that pretreatment with baicalin (i.p.) at concentrations of 0.5 and 5 mg/kg for 5 days before a single i.p. dose of t-BHP (0.1 mmol/kg) significantly lowered the serum levels of hepatic enzyme markers (ALT and AST) and reduced oxidative stress in the liver. Histopathological evaluation of the rat livers revealed that baicalin reduced the incidence of liver lesions induced by t-BHP including hepatocyte swelling, leukocyte infiltration, and necrosis. Based on the results described above, we speculate that baicalin may play a chemopreventive role via reducing oxidative stress in living systems.