Proteinase-activated receptor-2 (PAR-2) belongs to a novel subfamily of G protein-coupled receptors with seven-transmembrane domains. PAR-2 is activated by serine proteases, such as trypsin, mast cell tryptase, and allergic or bacterial proteases. The presence of trypsin has been shown in human stomach. Cyclooxygenase-2 (COX-2) is induced by inflammatory cytokines, growth factors, gastrin, and reactive oxygen species in gastric epithelial cells, which may lead to mutagenesis and subsequent metaplasia, dysplasia, and cancer formation. We investigated whether PAR-2 is activated in H. pylori (HP99)-infected cells, which is related to COX-2 induction in gastric epithelial cells. After treatment of H. pylori to AGS (gastric adenocarcinoma) cells at a bacteria/cell ratio of 100:1, we determine the expression and the activation of PAR-2 and the expression of COX-2. The same experiments were performed in the cells treated with PAR-2 agonist peptide. mRNA and protein expression of PAR-2 and COX-2 were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. PAR-2 activation was assessed by increase in intracellular calcium level. As a result, H. pylori induced the activation and expression of PAR-2 as well as COX-2 expression. PAR-2 agonist peptide augmented H. pylori-induced COX-2 expression in AGS cells. H. pylori induces COX-2 expression, which is mediated by both activation and expression of PAR-2 in gastric epithelial cells.