Objective To establish a mouse model of H. pylori infection, and to evaluate the chronic pathological changes in the gastric mucosa associated with H. pylori infection. Methods 34 male 5~6-week old SPF C57BL/6 mice were used in this study. The mice were intragastrically administrated with a suspension of H. pylori SS1 strain. Two weeks after infection, rapid urease test and PCR were performed to confirm the H. pylori infection. Successfully infected mice were randomly divided into 3 groups including the control group, 6-week and 12-week infected groups. Samples of gastric mucosa were taken for pathological analysis using HE and borax methylene blue staining. The contents of myeloperoxidase (MPO), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT) in the gastric tissues were detected by biochemistry, and the expression levels of COX-2, iNOS, TNF-α and IL-1β were examined by RT-qPCR. Results Compared with the control group, H. pylori colonization was observed in the gastric mucosa of the 6-week and 12-week infected mice, with chronic inflammatory cell infiltration, glandular atrophy and intestinal metaplasia to varying extents. The contents of CAT and SOD were significantly decreased, while the levels of MPO and malonaldehyde MDA, and the expression levels of COX-2,iNOS,TNF-α and IL-1β were significantly increased (P<0.05 or P<0.01). Conclusions Intragastric administration with H. pylori in C57BL/6 mice can be successfully used to generate the bacterial colonization, leading to chronic inflammatory cell infiltration, enhanced oxidative stress, and up-regulated expression of proinflammatory genes in the gastric glandular tissues at 6 and 12 weeks after inoculation. However, the inflammatory changes are more extensive in the mice at 12 weeks after infection, with glandular atrophy and intestinal metaplasia.