Monocytes/macrophages are known to be involved in atherogenesis, and the adherence of monocytes to the endothelium is considered an earliest characteristic of atherogenesis. Therefore, we studied the mechanism by which Shosaikoto, a Kampo medicine, shows anti-atherosclerotic action, which has been already shown in hypercholesterolemic rabbits. Hypercholesterolemia in rabbits gradually reduced the monocyte number in peripheral blood, whereas Shosaikoto treatment suppressed this decrease in circulating monocytes. Furthermore, although monocytes from hypercholesterolemic rabbits increased in adherence to endothelial cells even without lipopolysaccharide (LPS) activation, Shosaikoto treatment reduced the enhanced adherence observed in monocytes from hypercholesterolemic rabbits. These data suggested that the anti-atherosclerotic action shown by Shosaikoto resulted partly from the suppression of the enhanced adherence characteristic of hypercholesterolemia.