The aim of the present study was to investigateresponses from the gastric mucosa of rats duringlong-term H. pylori infection. Twenty-fourSprague-Dawley rats were inoculated with a mouse-adaptedstrain of human H. pylori (vacA⁺,cagA⁺), 16 uninfected rats served ascontrols. Three to six rats from each group were killedtwo weeks or two, six, or 12 months later. At sacrifice,blood was sampled and the gastric mucosa was taken for bacterial culture,histology, immunocytochemistry and in situhybridization. H. pylori colonized the antrum in 23/24inoculated rats; with time the density of bacteriaincreased. The inflammation in the antral mucosa was mildto moderate and was dominated by infiltration oflymphocytes and macrophages. Serum H. pylori-specificIgG_2a was significantly increased in theinfected rats. The frequency of epithelial cell apoptosis wassignificantly increased in the early months ofinfection. The mucosal expression of trefoil peptidemRNA remained unchanged. We conclude that after one year of H. pylori infection in rats, themucosal responses were rather mild, indicating that theanimals may adapt to the infection by mechanisms whichremain to be identified.