Recently, the four-kind cloning of the protease-activated receptor (PAR) had been carried out. PAR-2 is activated by trypsin and it is supposed that PAR-2 participated in proliferation of the endothelial cell or in neovascularization. We considered whether the expression of PAR-2 has relevance to progression in gastric cancer.Immunohistochemical study by the envision method was carried out on 183 samples of gastric cancer in the first department of surgery, University of Fukui, using anti-PAR-2 mouse monoclonal antibody and on 95 samples of them that were pointed out advanced gastric cancers by pathological diagnosis using anti-trypsin rabbit polyclonal antibody. Tissues, which were stained more than 20% of the tumor cells, were classified as PAR-2 protein-positive. Correlation with immunostainings and clinicopathological factors was analyzed statistically.There were 77 (42.1%) carcinomas positive for PAR-2 expression. The PAR-2 expression was intensely strong on the cell membrane of primary cancer tissues. The expression of PAR-2 correlated with the depth of wall invasion, lymphatic invasion, venous invasion, and liver metastasis. The patients with PAR-2 expression-positive tumors had a significant poorer prognosis than those with expression-negative tumors. Univariate analyses identified PAR-2 expression as negative predictors. Multivariate analyses indicated that PAR-2 expression was not an independent factor. A positive reaction for trypsin was obtained in 45 (47.4%) patients. We found a significant correlation between PAR-2 immunostaining and trypsin immunostaining.The results of this study lead us to believe that expression of PAR-2 is concerned with progression of gastric cancer.