Urinary trypsin inhibitor (UTI), an inhibitor of urokinase plasminogen activator relevant to proteolytic processing from the inactive into the active form of platelet-derived growth factor-D (PDGF-D) to activate PDGF-betabeta receptor (PDGF-betabetaR), inhibited fetal bovine serum-stimulated migration of human malignant mesothelioma, with the extent varying among the cell types. The more effective inhibition was found in NCIH-2052 and -2452 cells, with the higher expression of PDGF-betabetaR. The results of the present study suggest that UTI suppresses malignant mesothelioma cell migration by neutralizing active dimer of PDGF-D (PDGF-DD)/PDGF-betabetaR-mediated signal transduction.