AIM: To explore different ways of Helicobacter pylori animal model of infection, the H.pylori colonization and the pathogen of stomach were evaluated. METHODS: C57BL/6 mice were oral gavage with H. pylori suspension and the blank control was administrated with BHI equally. Two week later, PCR and RUT experiments were adopt to validate the H.pylori infection status. Next, the infected mice were randomly divided into 3 groups including control, 6-week and 12-week infected groups. After 6 weeks and 12 weeks’ infection, the stomach was removed for pathological examination, oxidative stress related enzymes and pro-inflammatory genes expression detection. RESULTS: Compared with the control, stomach mucosa layer was observed with monocytes infiltration. In 12-week infected group, the reduction of gastric inherent glands, the increment of fibrous, atrophy and intestinal metaplasia were all observed in the rat stomach. And the oxidative stress related enzymes of superoxide dismutase (SOD) and catalase (CAT) were decreased, meanwhile myeloperoxidase (MPO) and malonaldehyde (MDA) were obvious increased (P<0.05 or P<0.01); The gene expressions of COX-2，iNOS，TNF-α and IL-1β in 6-week and 12-week infected group were significantly increased (P<0.05 or P<0.01). CONCLUSIONS: C57BL/6 mice infected with H. pylori for 6 and 12 weeks can result in chronic inflammatory cell infiltration, enhance the levels of oxidative stress related enzymes and inflammation-related gene expressions up-regulation, of which 12-week infection presented with glandular atrophy and intestinal metaplasia.