BACKGROUND Postoperative peritoneal adhesion formation causes a multitude of disorders, including bowel obstruction and infertility. METHODS To test whether fibrin sealant inhibits adhesion formation, mice were given an intraperitoneal injection of talc (to induce adhesions) after which sealant was administered. Seven and 14 days later, the thickness of connective tissue between the fragmented mesothelium and the abdominal muscle was measured. RESULTS At both 7 and 14 days after talc administration, talc-treated mice had a 6-fold increase in connective tissue thickness over vehicle alone (P < .05). Although fibrin sealant alone failed to trigger peritoneal pathologic conditions, administration of sealant to talc-treated mice inhibited connective tissue deposition by 80% at 7 and 14 days (P < .05). Additionally, delaying fibrin sealant administration up to and including 72 hours after talc treatment results in comparable inhibition of connective tissue deposition, as does treatment immediately after talc exposure. CONCLUSIONS This study demonstrates that fibrin sealant inhibits peritoneal inflammation and peritoneal adhesion formation with use of a quantitative assay of connective tissue deposition. In addition, this is the first report to document the administration of fibrin sealant into the closed abdomen. The success of these studies suggests that fibrin sealant will block peritoneal adhesions when administered laparoscopically. Finally, because fibrin sealant is therapeutic even when administered after the initiation of peritoneal inflammation, it suggests that it may be efficacious in patients who present with adhesions or those undergoing multiple operations.