Our study evaluated the possible therapeutic effect of urokinase in treating the microthrombiotic effects of disseminated intravascular coagulation by assisting the activation of endogenous plasminogen. Twenty-six pigs were anesthetized, intubated, mechanically ventilated, and surgically catheterized. Septic shock was induced in all 26 pigs by an intravenous infusion of heat-killed Escherichia coli. The pigs were divided into two sets of experiments: in experiment 2 (n = 14), one-half received an intravenous dose of urokinase 1 h after heat-killed E. coli infusion and in experiment 3 (n = 12) one-half received an intravenous bolus dose and a continuous drip of urokinase 2 h after heat-killed E. coli infusion. The untreated pigs served as controls. Hemodynamic parameters, blood chemistries, and blood gases were analyzed. Urokinase given 1 h after bacterial toxin infusion significantly restored blood flow, resulting in an increase in cardiovascular and pulmonary function and improved survival rate (43% control vs. 100% treated, 24-h experimental period). Treatment given after 2 h showed some significant effect on pulmonary function; however, within 10 h of E. coli infusion, mortality rates in control and treated groups were 100 and 83%, respectively. Early administration of urokinase after onset of disseminated intravascular coagulation restored blood flow and helped resolve organ damage.