Midkine is a heparin-binding cytokine or growth factor and promotes the migration of inflammatory leukocytes. Upon partial hepatectomy, adhesion of the intestine was less severe in midkine-deficient mice than in wild-type mice. In a newly developed assay, in which the omentum adhered to the injured peritoneal wall, the incidence of adhesion in the deficient mice was reduced to 20% of that in the wild-type mice. Administration of midkine to the deficient mice increased the frequency of adhesion. The area of adhesion was also reduced to 8.3% in the deficient mice. The extent of migration of macrophages and neutrophils in the omentum around the adhesive region was reduced in the deficient mice. Therefore, midkine was concluded to play important roles in the formation of intraperitoneal adhesions, at least partly by promoting the migration of macrophages and neutrophils to the omentum. (C) 2004 Elsevier Inc. All rights reserved.