Abstract Porphyromonas gingivalis protease, which had been isolated from a culture supernatant, caused vascular permeability enhancement in a dose-dependent manner when injected into guinea pig skin. The permeability-enhancing reaction caused by the protease was not affected by treatment with antihistamine, but was greatly augmented by simultaneous injection of a kinin potentiator, carboxypeptidase N inhibitor. However, the reaction was inhibited by soybean trypsin inhibitor or α2-antiplasmin, although both of these inhibitors could not inhibit P. gingivalis protease at all by themselves. A bradykinin-degrading enzyme, carboxypeptidase B, weakened this vascular reaction. Results described indicate that the permeability-enhancing reaction induced by the protease is caused by activation of the kallikrein-kinin cascade in the tissue.