Cholestyramine (Colestyramine) is a bile acid binding resin and can inhibit intestinal bile acid absorption which results in the increasing bile acid synthesis from cholesterol. Results reveal that GSPE treatment alone, and co-administration with Cholestyramine (Colestyramine), regulate BA, cholesterol and TG metabolism differently compare to Cholestyramine administration alone. Notably, GSPE decreases intestinal apical sodium-dependent bile acid transporter (Asbt) gene expression, while Cholestyramine significantly induces expression. Administration with GSPE or Cholestyramine robustly induces hepatic BA biosynthetic gene expression, especially cholesterol 7α-hydroxylase (Cyp7a1), compare to control, while co-administration further enhances expression. Treatment with Cholestyramine induces both intestinal and hepatic cholesterologenic gene expression, while co-administration with GSPE attenuates the Cholestyramine-inducing increase in the liver but not in the intestine. Cholestyramine also induces hepatic lipogenic gene expression, which is attenuated by co-administration with GSPE.