The inhibition of nitric oxide (NO) and cyclooxygenase-2 (COX-2) production is considered to be a promising approach to the treatment of various diseases, including inflammation and cancer. In this study, we examined the effects of the Agrocybe chaxingu $eta$-glucan (polysaccharide) on lipopolysaccaride (LPS)-induced nitric oxide (NO) and cyclooxygenase-2 (COX-2) expression in murine macrophage Raw 264.7 cells as well as 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. The polysaccharide significantly inhibited (P < 0.01) LPS-induced iNOS and COX-2 expression levels in the cells. Furthermore, topical application of polysaccharide resulted in markedly inhibited (P < 0.01) TPA-induced ear edema in mice. These results suggest that this polysaccharide may be used for NO- and COX-2-related disorders such as inflammation and cancer.