Mannan interacts with mannose/N-acetylglucosamine (GlcNAc) receptors on the surface of both Kupffer cells and endothelial cells in the liver, and induces glycogenolysis through production of peptide-leukotriene (LT) in the perfused rat liver. In the present study, we examined whether positively and negatively charged GlcNAc-containing polysaccharides stimulate glycogenolysis in perfused rat liver. Infusion of the former, 67% deacetylated chitin (DAC), induced biphasic increases in glucose production and a steep decrease in oxygen consumption by the liver. ONO-1078, an LT D4 receptor antagonist, abolished the suppression of oxygen consumption and reduced the glucose production by DAC. Infusion of the latter, hyaluronan, stimulated glucose production with a concomitant increase in oxygen consumption. Ibuprofen, a cyclooxygenase inhibitor, reduced the glucose production by hyaluronan. Sequential infusions of mannan and DAC, but not hyaluronan, did not induce glycogenolytic responses when mannan was infused 20 min before the second stimulation. These results suggest that DAC, but not hyaluronan, stimulates mannose/GlcNAc receptors in the perfused rat liver, and that potent immunological activity induced by DAC may be mediated by activation of the receptors.