Background: Previous observations have shown vasoactive intestinal peptide (VIP) to be an important secretagogue in the gut, whereas somatostatin has been reported to inhibit VIP release and fluid secretion. Methods: The possible role of VIP as mediator of the inflammation and fluid losses in obstructive ileus was investigated in vivo in a chronic rat model with thread ligation of the jejunum. Extravasated Evans blue (Eb)-stained albumin was quantified by spectrophotometry. Net fluid secretion was measured by a gravimetric technique. VIP antiserum was used to inhibit the effects of endogenous VIP. A somatostatin analogue, octreotide, was used to inhibit the release of VIP. Results: Results showed a pronounced plasma Eb-albumin extravasation in the wall of the obstructed gut, which was significantly inhibited by VIP antiserum (p < 0.05) or octreotide (p < 0.01). Obstruction of the jejunum resulted in net fluid secretion that was significantly reduced by administration of octreotide (p < 0.01) or VIP antiserum (p < 0.05). Net fluid secretion in control animals remained constant. Conclusions: These findings suggest that VIP is an important mediator of the pathophysiology in mechanical intestinal obstruction and that somatostatin may be involved in the endogenous control of fluid losses.