Objective: The aim of this study is to determine whether a changed expression ratio of PAR-1 and PAR-2 in the colon is associated with diarrhea-predominant IBS patients. Methods: PAR-1, -2, thrombin, mast cell tryptase, tryptophan hydroxylase (TPH), and chromgranin A (ChrA) in colonic biopsy samples from 10 diarrhea-predominant IBS patients and 13 healthy control subjects were semiquantified with immunofluorescence and image analysis. Serotonin concentrations in biopsy samples were evaluated by capillary electrophoresis. Results: Significantly lower expression of PAR-1 and higher expression of mast cell tryptase was detected in the colons of patients, with statistically unchanged expression of PAR-2. Thrombin-, TPH-, and ChrA-positive cells were markedly increased in IBS patients, but no significant difference in serotonin concentration existed in the colons between two groups. The ratio of PAR-1/PAR-2 expression was significantly decreased in patients (0.33 ± 0.19 versus 0.66 ± 0.22, P = 0.001) and negatively correlated to ChrA-positive cells. Conclusions: Changed expression ratio of PAR-1 to PAR-2 in the colon is connected with diarrhea-predominant IBS patients. Methods to restore an appropriate balance of PAR-1 and PAR-2 activation in the colon may offer a promising future therapeutic strategy for IBS patients. © Springer 2009.