Hypercholesterolemia is known to enhance the risk of coronary heart disease and fatty liver. Colestimide is an anion-exchange resin, which is not absorbed in the small intestine, decreases the intestinal reabsorption of bile acids synthesized from cholesterol in the liver and consequently increases bile acid excretion into the feces. Bofu-tsusho-san, a traditional Japanese herbal remedy, contains 18 components and has long been used as an anti-obesity agent. In the present study, we investigated the effects of colestimide and/or Bohu-tsusho-san in young male mice fed a high-fat diet. The high-fat diet supplemented with both colestimide and Bofu-tsusho-san markedly reduced the plasma levels of lipids, the liver weight and number of fatty droplets in the liver cytoplasm, and the body growth, compared with animals fed a high-fat diet alone. Neither medicine affected the blood biochemistry. Thus, the hypocholesterolemic action of colestimide, sometimes bringing light flatulence, which is improved by simultaneous administration of Bofu-tsusho-san, which activates the thermogenesis of brown adipose tissue, is suggested to reduce body mass and liver lipids, lowering the plasma levels of lipids.