Potent acid inhibition with proton pump inhibitors (PPIs) is widely used in clinical medicine, especially for gastroesophageal reflux disease. PPIs cause profund changes in the intragastric environment with near-neutral pH, and increase serum concentration of the gastric secretagogue hormone gastrin. Long-term hypergastrinaemia increases mucosal thickness and ECL cell density in gastric corpus mucosa, and results in development of gastric carcinoids in experimental animals. Our aim was to study responses to potent acid inhibition by characterising genome-wide gene expression changes in gastric corpus mucosa in rats dosed with the PPI omeprazole. Nine rats received 400 µmol/kg omeprazole daily for 10 weeks. Seven rats received vehicle only. Analysis of gastric corpus with microarrays representing 11848 genes identified 134 genes with changed gene expression levels in omeprazole-dosed rats. Several of the identified genes were previously known to be affected by potent acid inhibition. Of the 62 genes with known functions that changed gene expression levels after PPI dosing, 27 are known to be involved in proliferation, apoptosis, immune-, inflammatory- and stress responses. Our study indicates that microarray analysis can detect relevant gene expression changes in the complex gastric tissue, and that cellular processes involved in cell growth and defence responses are strongly affected by PPI dosing. Many genes are identified that were not previously known to be affected by inhibition of gastric acid secretion or that have unknown biological functions. Characterisation of the roles of these genes may give new insight into molecular responses to treatment with PPIs.