AIM: To establish a stable and reliable model of Helicobacter pyloriinfection model in Mongolian gerbils and to observe pathological changes in gastric mucosa in infected animals. METHODS: Mongolian gerbils were randomly divided into 18 groups; 6 groups were infected with Hpylori clinical strain Y06 (n=6, groups Y), 6 groups were infected with H pylori strain NCTC11637 (n=6, groups N), and 6 uninfected groups as negative controls (n=4,, groups C). Hpylorisuspensions at the concentrations of 2 x 108 and 2x 109 CFU/mL of strain NCTC11637 and strain Y06 were prepared. The animals in three groups N and in three groups Y were orally challenged once with 0.5 mL of the low concentration of the bacterial suspension. The animals in another three groups N and in another three groups Y were orally challenged with 0.5 mL of the high concentration of the bacterial suspension for 3times at the intervals of 24 h, respectively. For the negative controls, the animals in six groups C were orally given with the same volume of Brucella broth at the corresponding inoculating time. The animals were killed after 2nd, 4th and 6th week after the last challenge and the gastric mucosal specimens were taken for urease test, bacterial isolation, pathological and immunohistochemical examinations.RESULTS: Positive isolation rates of Hpyloriin the animals of groups Y at the 2nd, 4th and 6th week after one challenge were 0%, 16.7% and 66.7%, while in the animals of groups N were 0%, 0% and 16.7%, respectively. Positive isolation rates of H pyloriin the animals of groups Y at the 2nd, 4thand 6th week after three challenges were 66.7%, 100% and 100%, while in the animals of groups N were 66.7%, 66.7% and 100%, respectively. In animals with positive isolation of Hpylori, the bacterium was found to colonized on the surface of gastric mucosal cells and in the gastric pits, and the gastric mucosal lamina propria was infiltrated with inflammatory cells.CONCLUSION: By using H pylori suspension at high concentration of 2 × 109 CFU/mL for multiple times, the orally challenged Mongolian gerbils can be used as a stable andreliable H pylori infection model. The 2 strains of H pylori can colonize in gastric mucosa of the infected animals and cause mild inflammation reaction.