【Abstract】 Objective To observe the effects of different ligation sites and fasting methods on a C57BL/6J mouse model of partial bile duct ligation (pBDL) induced cholestasis, and study a pBDL modeling method with high modeling rate, typical symptoms, and good stability. Methods C57BL/6J mice were subjected to left bile duct ligation (L-pBDL) and left to median bile duct junction ligation (ML pBDL) for modeling, and the effects of different pBDL ligation methods on serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), total bile acid (TBA), and liver histopathology of the model were observed; And the effects of different fasting methods on the symptoms and liver injury of the ML-pBDL model were observed by fasting for 12 and 16 hours before surgery, and fasting and fasting for 4 hours after surgery. Results (1) The incidence of jaundice in the ML-pBDL group was 52.94%, and the survival rate within 3 weeks after surgery was 64.71%, while the incidence of jaundice in the L-pBDL group was 11.76%, and the survival rate within 3 weeks after surgery was 82.35%; Compared with the sham surgery group, the serum liver function indicators in the L-pBDL group and the ML-pBDL group were significantly increased (P<0.01), and the ALP activity in the ML-pBDL group was significantly higher than that in the L-pBDL group (P<0.05); Compared to the L-pBDL group, the ML-pBDL group had more severe liver fibrosis at 3 weeks post surgery (P<0.01). (2) The incidence of jaundice in the 16 hour fasting group was 93.33%, and the survival rate within 3 weeks after surgery was 73.77%. However, the incidence of jaundice in the 12 hour fasting group was 42.86%, and the survival rate within 3 weeks after surgery was 71.42%; Compared with the normal group, the ALP activity, ALT/AST ratio, TBA level, and proportion of collagen fiber area were significantly increased in the 16 hour and 12 hour fasting groups (P<0.05) The observed indicators in the 16 hour fasting group were higher than those in the 12 hour fasting group, but there was no significant difference (P>0.05). Both the 12 hour and 16 hour fasting groups showed significant bile duct hyperplasia and liver fibrosis (P<0.01), and the liver fibrosis in the 16 hour fasting group were more severe (P<0.01). Conclusion Both L-pBDL and ML-pBDL ligation methods can establish a mouse model of cholestasis. However, the symptoms of the L-pBDL model only exhibit transient damage characteristics, while the liver lesions of the ML-pBDL model are typical and stable. Prolonging preoperative fasting time can improve the modeling rate and stability of the ML-pBDL model, and the pathological symptoms are more typical.