Abstract: The protective effects of chitosan oligosaccharide (COS), d-glucosamine (GlcNH2) and N-acetyl-d-glucosamine (GlcNAc) on carbon tetrachloride (CCl4)-induced hepatotoxicity and the possible mechanisms that involved were investigated in male ICR mice. CCl4 (20mg/kg body weight, i.p.) administration induced marked increase in serum AST and ALT activities, primed liver lipid peroxidation, depleted sulfhydryl content, impaired total antioxidant capabilities and induced genotoxicity 24h after administration. Pretreatment with COS, GlcNH2, and GlcNAc (1.5g/kg body weight, i.g.) for 12 consecutive days prior to CCl4 challenge significantly induced metallothionein (MT) expression. Thus, the antioxidant defensive system in the body was strengthened to counteract the oxidative damage induced by the succedent CCl4 administration. Serum AST and ALT activities were effectively decreased. Hepatic malondialdehyde formation was inhibited and sulfhydryl contents, total antioxidant capabilities were markedly restored. Genotoxicity as reflected by DNA fragmentation, however, was not mitigated by pretreatment with COS, GlcNH2, and GlcNAc. Histophathologic results of liver also confirmed their hepato-protective effects. Pretreatment with COS, GlcNH2, and GlcNAc also could significantly decrease serum creatinine and uric acid levels and inhibit lipid peroxidation in kidney homogenate. Our results suggest that pretreatment with COS, GlcNH2, and GlcNAc can efficiently protect mice against CCl4-induced toxicity. [Copyright &y& Elsevier]