The mushroom Coriolus versicolor contains biologically active polysaccharides, most of which belong to the beta-glucan group. Diverse physicochemical properties, due to different sources and isolated types of beta-glucans, can induce distinct biological activities. We investigated the effects of beta-glucans from C. versicolor on phagocytic activity, nitric oxide (NO), TNF-alpha production, and signaling of dectin-1, a well-known beta-glucan receptor, in macrophages. beta-Glucans increased phagocytic activity and TNF-alpha and NO-iNOS/eNOS production. Laminarin, a specific inhibitor of dectin-1, showed strong inhibitory effects on phagocytosis and subsequent TNF-alpha, iNOS, and eNOS production increased by beta-glucans, indicating that beta-glucans reacts with dectin-1 receptors. We examined whether the aforementioned cytokines were involved in the signaling pathway from the dectin-1 receptor to phagocytosis, and found that the inhibition of iNOS, eNOS, and TNF-alpha receptors significantly decreased beta-glucan-induced phagocytosis. In conclusion, our study showed that dectin-1 signaling, triggered by beta-glucans, subsequently elicited TNF-alpha and NO-iNOS/eNOS production, and that these molecules seem to act as secondary molecules that cause eventual phagocytosis by macrophages. These findings suggest that C. versicolor could be used as a nutritional medicine that may be useful in the treatment of infectious disease.