Objective:To observe the protective effect of cuttlebone polysaccharides (CBP-s) on gastric mucosa lesions induced by absolute ethanol in mice,and to study the related mechanism.Methods:Mice were pretreated by CBP-s for 3 or 5 days and then were administered with absolute ethanol orally to induce gastric mucosa lesions.Then the ulcer index,pH value of gastric contents,the levels of nitric oxide (NO),malondialdehyde (MDA),reduced glutathione (GSH),and the activity of SOD in the gastric mucosa were studied.Results:Mice gastric ulcer indices decreased after pretreated with 100 mg/kg,200 mg/kg,and 400 mg/kg CBP-s for 3 or 5 days.The pH values of gastric contents after 3 day-pretreatment were 3.09±0.20,3.32±0.15,3.38±0.15,and after 5 day-pretreatment were 3.43±0.23,3.34±0.25,3.68±0.24,respectively.MDA contents of gastric mucosa after 3 day-pretreatment with 400 mg/kg CBP-s and after 5 day-pretreatment with all 3 concentrations were (125.41±28.79),(145.80±26.13),(153.88±21.19),and (127.14±5.68) nmol/g,respectively,all significantly lower than that of the model group (P<0.05).GSH and NO contents were significantly increased in all but 100 mg/kg for 3 days group (GSH:\[282.93±32.33\],\[293.57±20.76\],\[260.79±39.23\],\[253.71±21.11\],\[359.38±10.89\] mg/g,P<0.05),(NO:\[23.40±4.41\],\[25.83±4.89\],\[21.60±3.05\],and \[22.75±2.44\] μmol/g,P<0.05).The activities of SOD were significantly increased in all groups (\[30.61±6.37\],\[45.35±1.90\],\[47.12±4.68\],\[36.48±5.64\],\[41.38±8.23\],and \[39.42±8.76\] U/mg,P<0.05).Conclusion:Our results indicate that CBP-s can protect ethanol-induced gastric mucosa from injury in mice.