The purpose of this study was to investigate the preventive effects of Paeoniae Radix Extract (PRE) against the acute hepatotoxicity-inducing lipopolysaccharide (LPS) in the liver. PRE of 100 mg/kg concentration was intraperitoneally administered into rats at dose of 1.5 ml/kg for 20 days. On day 21, 5 mg/kg of LPS dissolved in saline was injected 4 hours before anesthetization. We examined the levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), lactate dehydrogenase (LDH) in serum of rats, superoxide dismutase (SOD) in mitochondrial fractions, and malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPx) in liver homogenates. LPS-treatment markedly increased the levels of GOT, GPT, LDH and MDA, and significantly decreased those of SOD, CAT and GPx. But PRE-pretreatment decreased the levels of GOT, GPT, LDH and MDA, by 59.7%, 43.6%, 59.6% and 63.5%, respectively and increased those of SOD, CAT and GPx, by 85.5%, 57.8% and 62.9%, respectively. These results showed that the PRE had the preventive effects against the acute hepatotoxicityinducing LPS in the liver .