Introduction Urinary trypsin inhibitor, a serine protease inhibitor, has been widely used, particularly in Japan, as a drug for patients with acute inflammatory disorders such as pancreatitis, shock and disseminated intravascular coagulation. Previous in vitro studies have demonstrated that serine protease inhibitors may have anti-inflammatory properties beyond their inhibition of neutrophil elastase at sites of inflammation. However, the therapeutic effects of urinary trypsin inhibitor in vivo remain unclarified. In this review, we introduce the roles of urinary trypsin inhibitor in experimental systemic inflammatory responses induced by both the intraperitoneal and intratracheal administration of lipopolysaccharide using urinary trypsin inhibitor-deficient (-/-) and corresponding wild-type mice. Conclusion Urinary trypsin inhibitor may provide an attractive 'rescue' therapeutic option for systemic inflammatory response syndromes such as disseminated intravascular coagulation, acute lung injury and acute liver injury.