Glucagon-like peptide 2 (GLP-2) is a potent intestinotrophic peptide that enhances recovery following intestinal injury. We tested the hypothesis that GLP-2 acutely enhances intestinal epithelial restitution.Rat jejunal segments were mounted in Ussing chambers. HCl (10 mM) was applied to the mucosal surfaces for 10 min to induce injury. Tissues were then lavaged with modified Ringer's solution and maintained in the chambers for an additional 3 h. Tissues were treated with 10 microM GLP-2 or vehicle alone (control). Electrical parameters were recorded, and tissues were salvaged for morphometric analysis.GLP-2-treated tissues exhibited a significantly greater recovery of potential difference and resistance (P < 0.05) than did controls. Morphometric analysis revealed that columnar cells covered a greater percentage of the epithelial surface in GLP-2-treated tissues than in controls (P < 0.05).These results suggest that GLP-2 acutely enhances intestinal epithelial restitution following acid-induced injury. This novel biological action of GLP-2 may contribute to its therapeutic effect in models of intestinal disease.