Burn injury produces acute gastrointestinal (Gl) derangements that may predispose the burn victim to bacterial translocation (BT). We studied the effects of heparin on gastrointestinal (Gl) anatomic alterations and BT after 25% and 32% total body surface area (TBSA), full-thickness murine burn injuries. Heparin (100 U/kg) was administered with 1 mL of normal saline (NS) resuscitation solution immediately postburn and 4 hours and 18 hours postburn in volumes of 0.5 mL NS. Mice with 25% TBSA burns treated with heparin maintained small intestine weight, measured 24 hours postburn, and ileal mucosal height was preserved, whereas burned, untreated mice lost organ weight and mucosal height. Bacterial translocation was decreased in mice with 25% TBSA burn injuries treated with heparin (35.0% vs. 10.7%, p < 0.025). After 32% TBSA burn injuries, BT was also decreased in heparin-treated animals (64.3% vs. 31.6%; p < 0.025). Analysis of mixed venous blood gases showed that heparin did not affect the severe metabolic acidosis that follows burn injury in this animal model, indicating that general tissue perfusion was not improved. Heparin administered in the acute postburn period ameliorates Gl structural and functional damage in this murine burn model and decreases BT.