Central venous catheters are commonly used in clinics for the administration of infusion therapy and total parenteral nutrition. Catheter occlusion is the most common noninfectious complication associated with the long-term use of such devices. The cause of catheter occlusion is the formation of a tissue sleeve around the catheter. In this study, a rat model was used to investigate the effects of integrin antagonist peptide on the growth of the tissue sleeve around the jugular catheters. When integrin antagonist peptide was injected subcutaneously, twice daily, for 3 days, at a dosage of 10 mg/kg of body weight/day, the growth of the tissue sleeve was reduced by 40%, as compared to rats injected with saline or control peptide. Morphological study of the tissue sleeve indicated that catheter-related damage to the nearby endothelial cells was associated with the adhesion of platelets and leukocytes to the injured endothelium and accumulation of fibrin in the vicinity. This proposed sequence of events resulted in an increase in the thickness of the tissue sleeve and changes in sleeve transparency.