Introduction: Fibrin glue is used in the endoscopical therapy of bleeding ulcerations in the upper gastrointestinal tract. Aim of the present study was to elucidate biological effects of fibrin glue with regard to healing in a human model of gastric ulcer. Methods: Gastric lesions were induced by biopsy forceps in H.pylori-negative subjects and subsequently treated by injection of equal volumes of either fibrin glue (Beriplast™, ZLB Behring, Liederbach, Germany) or isotonic saline. Three days later, the size of resulting ulcers was assessed and biopsies taken for histological and biochemical analysis. The density of proliferating cells and microvessels was analyzed by immunohistochemistry. mRNA expression of growth factors involved in gastric ulcer healing (PDGF-A/B, VEGF, FGF2) was determined by quantitative real-time RT-PCR. Results: After three days, most ulcers exposed to fibrin glue were smaller than those treated with saline. The ulcer rim was more pronounced. Immunohistochemistry revealed more proliferating cells (p<0.02 compared to saline) as a result of an extension of basal and apical proliferation zone. The number of small vessels increased as well but without reaching statistical significance (p = 0.10). FGF-2 mRNA expression markedly increased (about sevenfold increase compared to control [p<0.001], about fivefold compared to saline [p<0.015]), only small changes with respect to PDGF and VEGF mRNAs occurred. Conclusions: Fibrin glue modulates gastric ulcer healing, causes an increase in the number of proliferating cells in the ulcer margin, and possibly enhances the density of microvessels as well. These changes are accompanied by an enhanced expression of FGF-2, which is known to exert beneficial effects on the course of ulcer healing. This may explain, together with the reported accelerated closure of ulcers, the reduction of bleeding recurrences attributed to the use of fibrin glue.