Macrophages play important roles both in immune response and in lipid metabolism and contribute to the development of atherosclerosis. To clarify the mechanism by which Shosaikoto, a Kampo medicine, shows anti-atherosclerotic action, we studied its effect on macrophage function. The production of nitric oxide (NO), prostaglandin E2 and interleukin 1 by macrophages in mice was reduced by feeding of a cholesterol-enriched diet, and the reduced production was observed 1 week after the beginning of cholesterol feeding. Furthermore, although oxidized low density lipoprotein (LDL) and lysophosphatidylcholine (LPC) reduced NO production, macrophages prepared from mice treated with Shosaikoto at a dose of 1.2 g/kg/d restored the reduced NO production by them as well as by hypercholesterolemia. When the content of LPC was measured, no difference was observed between mice fed a cholesterol-enriched diet in the presence or absence of Shosaikoto treatment, suggesting that the restorative effect of Shosaikoto is not due to the inhibition of LPC production or accumulation. Conclusively, Shosaikoto prevents the modification of macrophage function induced by atherogenic factors, which is probably linked to its displayed anti-atherosclerotic action.