The objective of this study is to investigate the effects of two different yeast-derived beta-glucans on macrophage functionality and blood cholesterol levels in mice. After establishing their ability to act as a strong stimulator of macrophages, we measured the capacities of the glucans to lower blood cholesterol. Our results showed that consumption of diets containing yeast-derived beta-glucan indicated a dose-dependent decrease in plasma cholesterol levels, with Betamune having a significantly stronger effect than WGP (Whole Glucan Particles). In hypercholesterolemic subjects, the cholesterol- and triglycerides-lowering effects of Betamune were again significantly stronger. The results of this investigation demonstrated that highly purified yeast-derived beta-glucans modify plasma cholesterol levels and other indicators associated with artherogenic progression in mice. The fact that these glucans also strongly stimulated both monocytes and macrophages supports the hypothesis that there could be a macrophage-cholesterol (metabolism) axis involvement in these outcomes.