Abstract：Objective：To investigate the protective effect of luteolin on rats with severe acute pancreatitis(SAP)-related acute liver injury by reducing the expressions of cytochrome P4502E1(CYP2E1). Methods：A total of 50 male SD rats were divided into the sham operation group， the model group and the luteolin groups with low， medium and high dose respectively，10 rats in each group. Except for the sham operation group，the other groups were given the injection of 5% sodium taurocholate into the bile duct with a dose of 1.5 mL/kg at a uniform speed of 0.2 mL/min to prepare the SAP models， and the sham operation group was given the same amount of saline. Two hours before the model preparation，the luteolin groups with low， medium and high dose were intraperitoneally injected with 10.0 mg/kg， 20.0 mg/kg and 40.0 mg/kg of luteolin respectively；the sham operation group and the model group were given the same amount of saline. After 24 hours of model preparation， blood samples were collected from the heart to detect the levels of amylase(AMY)， alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in serum； the levels of tumor necrosis factor- α(TNF- α) and interleukin- 1β(IL- 1β) were detected by ELISA method； the levels of glutathione(GSH)， reactive oxygen species(ROS)， CYP2E1， high mobility group box protein 1(HMGB1)， toll- like receptor 4(TLR- 4)， and the antibody of phosphated interleukin-1 receptor-associated kinase 1(p-IRAK1) in the liver tissue were detected. Results：Compared with those in the sham operation group， the levels of AMY， ALT， AST， TNF- α， IL- 1β in serum and the expression levels of ROS， CYP2E1，HMGB1，TLR-4 and p-IRAK1 in the liver tissue in the model group were all increased(P＜0.05)，and GSH level in the liver tissue was decreased(P＜0.05). Compared with those in the model group，the levels of AMY，ALT，AST，TNF-α， IL-1β in serum as well as the expression levels of ROS，CYP2E1，HMGB1，TLR-4 and p-IRAK1 in the liver tissue in the luteolin groups with low，medium and high dose were all decreased(P＜0.05)，and GSH level in the liver tissue was increased (P＜0.05)， which showed a dose- dependent manner(P＜0.05). Conclusion： Luteosin can reduce SAP- related acute liver injury，and its mechanism may be related to the down-regulation of CYP2E1 expressions and the inhibition of HMGB1-TLR-4 signaling pathway.