Abstract: Objective To study the effect of aspirin and omeprazole on gastric mucosa injury and nitric oxide （NO） and tumor necrosis factor （TNF） level in blood of rats at different ages and its mechanism. Methods Eighteen healthy Wistar rats at the age of 3 and 22 months were randomly divided into normal control group, aspirin injury group and omeprazole protection group, 6 rats in each group. Rats in aspirin injury group, omeprazole protection group and normal control group underwent gastric lavage with aspirin, omeprazole and normal saline, respectively. Levels of NO and nitric oxide synthase （NOS） and activity of NOS, iNOS and cNOS were measured. Scores for gastric mucosa injury in different groups of rats were compared with Guth and Whittle methods. Results The Guth and whittle scores for injuries in group of aged rats were higher than those group of non-aged rats （P＜0.05）. The TNF and NO level and the iNOS activity were higher in aspirin injury group than in normal control and omeprazole protection groups. However, the activity of cNOS was lower in aspirin injury and omeprazole protection groups than in normal control group. The gastric mucosa injury was positively correlated with the activity of iNOS and the level of NO and TNF, but negatively correlated with the activity of cNOS. Conclusion Gastric mucosa of aged rats is more sensitive to injury factors while its repair ability decreases. The mechanism by which aspirin injures gastric mucosa of rats may be related with increasing iNOS activities, NO and TNF levels, and decreasing cNOS activities. Omeprazole protects gastric mucosa against injury by decreasing the TNF and NO level.