Objective: To investigate the function of cholic acid (CA) in liver regeneration of obstructive jaundice (OJ) following partial hepatectomy in mice and the mechanism. Methods: One hundred and eighty healthy male mice were equally randomized into 6 groups, and underwent sham operation (control group), common bile duct ligation (OJ group), common bile duct ligation followed by external drainage (ED)7 d later (ED group), common bile duct ligation plus 0.2%CA gavage followed by ED 7 d later (ED+0.2%CA group), common bile duct ligation plus 1%CA gavage followed by ED 7 d later (ED+1%CA group), and common bile duct ligation followed by internal drainage (ID) 7 d later (ID group), respectively. In the 14th day of experiment, partial (70%) liver resection was performed in each group of mice, and ID conversion was made in each group of mice with ED treatment. On different time points after hepatecomy, the liver regeneration rate and expression of proliferation-associated nuclear antigen Ki-67, mRNA expression of forkhead box M1b (Foxm1b), and protein expression of fibroblast growth factor receptor 4 (FGFR4) in the liver tissue were determined, and in situ apoptosis of hepatic cells was also observed in some of the groups. Results: Excluding the control group, the liver regeneration rate, Ki-67 positive expression rate, and Foxm1b mRNA as well as FGFR4 protein expression levels in the remaining groups were all presented in a decreasing order as follows: ID group>ED+0.2%CA group>ED group>OJ group>ED+1%CA group, and all inter-group differences had statistical significance (all P<0.05); there was no significant difference in any of the above parameters between ID group and control group (all P>0.05). The apoptosis rate of hepatic cells showed a decreasing order as follows: ED+1%CA group>ED group>ED+0.2%CA group>control group, and all inter-group differences had statistical significance (all P<0.05). Conclusion: ID is beneficial to liver regeneration after liver resection through reducing endogenous CA loss; low concentration of exogenous CA supplement can improve the liver regeneration retardation caused by ED, which may be associated with its up-regulating Foxm1b and FGFR4 expressions, and thereby promote liver regeneration.