Recent studies indicate that heparinization before hemorrhage maintains microvascular patency in the liver and kidney during and after severe hemorrhagic shock. However, it is not known whether preheparinization has any protective effects on organ function after hemorrhage and resuscitation. To study this, unanesthetized rats (with or without preheparinization) were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of the maximum shed blood volume was returned in the form of Ringer lactate (RL). They were then resuscitated with four times the volume of the shed blood with RL. Cardiac output (CO), [3H]inulin clearance (C(In); renal function), hepatic microvascular blood flow (HMBF), and hepatocellular function (HF), i.e., maximal velocity of indocyanine green clearance (V(max)), were determined 1.5 h after resuscitation. Although CO decreased in both groups, the values in preheparinized rats were significantly higher than in the nonheparinized rats. The improvement in C(In) as well as HMBF followed the same trends. HF (V(max)) was significantly depressed in the nonheparinized rats but was maintained in preheparinized rats. Thus administration of heparin before the onset of hemorrhage improves CO and renal function and restores HF to control after hemorrhage and resuscitation. These protective effects of preheparinization could be due to the maintenance of microvascular patency and prevention of blood sludging during and after hemorrhage.