Objective: To investigate the effect of Pioglitazone on genes involved in bile acid enterohepatic circulation in C57bl mice. Methods: C57bl mice were randomly divided into two groups, named NC (normal control, n=8) group and M (medicine, n=8) group, respectively. Mice in NC group were fed with chow diet, while mice in M group were fed with both Pioglitazone and chow diet, and the feeding last for 10 weeks. At the end of our experiment, all mice were sacrificed and blood samples,liver and intestine tissues were collected. Fully automatic biochemical analyzer was used for the detection of blood metabolic parameters, and qRT-PCR was used for the detection of gene expression，which were involved in bile acid enterohepatic circulation. Results: Mice in group M displayed an increased biliary BA content. FXR, CYP7A1 and CYP27A1，which play important roles in bile acid synthesis were detected in an induced expression in group M mice. Hepatic bile acid transporters BSEP and NTCP were also detected in an increased expression in group M compared with group NC. Immunohistochemical examination testified an increased protein expression of BSEP in mice liver tissue. ASBT, a gene regulates intestinal bile acid reabsorption, were detected in an increased expression in group M mice. Conclusion: Pioglitazone increased the expression of genes involved in bile acid synthesis, bile acid transport,as well as intestinal reabsorption,which indicates the drug，may play a great role in regulating genes involved in enterohepatic circulation.