The aim of our study was to investigate the protective role of chitooligosaccharides (COS) on dextran sulfate sodium (DSS)-induced colitis in mice,which might provide a theoretical reference for the development and utilization of COS.In this study,ulcerative colitis was induced by oral administration of 3% DSS for 7 days in drinking water.A total of 50 male C57BL/6 mice were randomly divided into 5 groups:control group,model group,positive control group with sulfasalazine (SASP,50 mg/kg),model group with a low dose of COS (70 mg/kg) and the high dose of COS (140 mg/kg).The protective effect of COS was assessed by weight change and disease activity index (DAI),colon length,histopathological scores and myeloperoxidase (MPO).Inflammation cytokines in colon tissue were detected by ELISA.COS supplement decreased weight loss,DAI and the MPO activities (P>0.05),also significantly reduced the levels of Interleukin (IL)-6,tumor necrosis factor (TNF)-α in the colon tissue,in DSS-treated mice (P<0.05).Additionally,70 mg/kg COS showed a significantly protective effect on colon length and colonic structure in response to DSS challenge (P<0.01),which was better than that of 140 mg/kg COS.In conclusion,COS (70 mg/kg,transferring from a recommended dosage of human) showed obvious protective effects against DSS-induced colitis,which may be associated with suppressed neutrophil infiltration and inflammation.