Based on the subacute toxicity test,the hepatotoxicity mechanism of different extracts of Sophora alopecuroides was studied to provide theoretical basis for the safe clinical use of S. alopecuroides. Extracts of  S. alopecuroides were prepared by 75% ethanol reflux method (ER),water decoction method (WD),75% ethanol ultrasonic method (EU) and water ultrasonic method (WU),respectively.The levels of alanine transaminase (ALT),aspartate transaminase (AST),superoxide dismutase (SOD),glutathione (GSH) and malondialdehyde (MDA) in liver tissue of rats were determined to evaluate subacute toxicity.The expression of nuclear factor erythroid-2 related factor 2 (Nrf2),heme oxygenase-1 (HO-1),superoxide dismutase-1 (SOD1),superoxide dismutase-2 (SOD2) were determined by immunohistochemistry and Western blotting to further explore the hepatotoxicity mechanism.Compared with the blank group,the results showed that AST significantly increased in the serum of male rats in each dosing group,and ALT increased in both male and female rats,especially in the male of WD,ER groups and the female of WD,WU and EU groups.Compared with the blank group,SOD and GSH in the liver of male rats decreased significantly in each group,GSH tended to increase in the liver tissue of female rats,with significant difference in the WD group,and MDA significantly increased in the liver of both male and female rats.After administration,the Nrf2/HO-1 oxidative stress pathway-related proteins were detected,and the expression of Nrf2 protein in liver tissues decreased compared with the blank group,with the most significant in the male WD,WU,EU and female WD,EU and ER groups,HO-1 expression in liver tissue was significantly decreased in both females and males.SOD1 significantly decreased in all groups of females,while significantly decreased in males of the WD and ER groups.In this study,different extracts of S. alopecuroides have some toxicity to rat liver,and its toxicity mechanism mainly occurred through oxidative stress caused by regulating the Nrf2/HO-1 pathway related proteins.