Summary Dietary soy protein isolate (SPI) and its undigested high molecular fraction (HMF) exhaustively digested with proteases, compared with casein (CAS), significantly reduced serum and liver cholesterol concentration in rats. Biliary excretion of cholesterol was significantly higher in rats fed SPI and HMF than in those fed CAS. Hepatic expression of ATP-binding cassette transporter G5 (ABCG5) and ATP-binding cassette transporter G8 (ABCG8) mRNA was significantly higher in rats fed SPI and HMF than in those fed CAS. These observations suggest that increased biliary excretion of cholesterol in SPI and HMF groups is caused by the enhanced expression of Abcg5/Abcg8. Key Words ATP-binding cassette transporter G5, ATP-binding cassette transporter G8, bile, cholesterol, soy protein isolate ATP-binding cassette transporter G5 (ABCG5) and ATP-binding cassette transporter G8 (ABCG8) are mainly expressed in the liver and the intestine ( 1 ). It has been suggested that ABCG5 and ABCG8 have a function to excrete sterols from intestinal cells to the intestinal lumen and from the liver to the bile ( 1 ). Although functions of ABCG5 and ABCG8 on sterol excretion gradually become apparent, the contribution of ABCG5 and ABCG8 to cholesterol metabolism in the whole body is not fully understood and scarcely any information on regulation of ABCG5 and ABCG8 expression by dietary components has been obtained.It has been reported that dietary soy protein isolate (SPI) and its undigested high molecular fraction (HMF) lower serum cholesterol concentration in experimental animals ( 2 -4 ). One of the mechanisms of hypocholesterolemic effects of SPI and HMF is an increase in fecal bile acid excretion ( 3 , 4 ). The increased excretion of bile acids can be caused by their binding with SPI and HMF ( 3 , 4 ). Fecal excretion of neutral steroids originated from cholesterol was also increased by the feeding of SPI and HMF in rats fed a high-cholesterol diet ( 3 -5 ). It has been thought that increased excretion of cholesterol and the metabolite coprostanol is caused by reduced availability of bile acids for the bile salt micelle in the intestinal lumen and therefore by reduced solubility of cholesterol in the micelle ( 3 , 4 , 6 ). Although increased fecal excretion of cholesterol and coprostanol can be caused by increased expressions of ABCG5 and ABCG8 in the liver and the intestine, no information is available about whether SPI and HMF influence expressions and functions of ABCG5 and ABCG8 in the liver and the intestine. In the present study, we examined effects of SPI and HMF on cholesterol metabolism in relation to mRNA expressions of ABCG5 and ABCG8 in the liver and the intestine of rats.