BACKGROUND/AIMS: Fibroblast growth factor-10 (FGF-10) is a homolog of keratinocyte growth factor-2 with epithelial mitogenic activity. We investigated the therapeutic role of FGF-10 in intestinal ulceration and its mechanism of protection. METHODS: FGF-10 was administered before or after induction of small intestinal ulceration by indomethacin. FGF-10 was injected subcutaneously (1 or 5 mg/kg) and intravenously (1 mg/kg) daily for 6 days (acute study). Injury was evaluated by double-blinded macroscopic and microscopic scores, and the concentration of tissue interleukin (IL)-1beta and the expression of collagen type I RNA were compared. It was determined whether FGF-10 has an effect on in vitro epithelial cellular proliferation, restitution of wounded monolayers, the expression of cyclooxygenase-2 (COX-2) and collagen, and regulation of NF-KB. RESULTS: Intravenous FGF-10 significantly decreased acute intestinal injury by all parameters. FGF-10 promoted in vitro proliferation and migration of epithelial cell, and stimulated COX-2 expression, but had no effect on IKB degradation. FGF-10 affected up-regulated collagen expression in cultured myofibroblasts but not in vivo fibrosis. CONCLUSIONS: FGF-10 treats intestinal inflammation by actively promoting the mechanism to heal epithelial cells.