The formation of intraperitoneal adhesions, the pathological adherence of organs and tissue surfaces, is the leading cause of postoperative intestinal obstruction following abdominal surgery, as well as the major contributing factor to infertility after reconstructive tubal surgery. At present, there is no generally accepted therapy for the prevention of adhesion formation. Since fibrin has been shown to be the physiological basis of adhesion formation, the current study was undertaken to determine if an application of exogenous rt-PA to the site of peritoneal injury would prevent adhesion formation. New Zealand white rabbits (3 kg) were anesthetized and midline laparotomies performed. A nine cm area of the peritoneal wall was surgically removed and resutured in place, creating an ischemic patch of peritoneal tissue. A proximal area of the cecum (75cm2 ) was abraided with dry gauze until punctate bleeding occurred. Approximately 2.5 grams of an ointment containing 0, 0.16, 0.31, or 0.63 mg rt-PA was applied to the ischemic peritoneal tissue and the abraided cecum. After seven days the rabbits were euthanized and the adhesions scored. In the rabbits which received placebo ointment (n=6) the cecum was adhered to the entire area of the ischemic patch. In the rabbits which received the ointment containing 0.63 mg of rt-PA, five had no adhesions and one rabbit had a very minor adhesion. The high dose of rt-PA was equally effective in preventing reformation of adhesions after surgical lysis. No evidence of systemic fibrinogen degradation or abnormal wound healing were evident in this model.In summary, these studies demonstrate that intraperitoneal administration of rt-PA is effective in preventing initial adhesion formation as well as the reformation of adhesions after surgical trauma or injury.