Annexin-1 (ANXA-1) is a 37 kDa protein implicated in the control of phagocytosis, cell differentiation and proliferation, and as a mediator of glucocorticoid action during inflammation. Moreover, ANXA-1 regulates leukocyte migration, ischemic damage, pain, as well as acute and chronic inflammation. These effects of ANXA-1 are mediated via formyl peptide receptors (FPR / FPRL-1), which are also activated by bacterially derived, chemotactic, formylated peptides. As ANXA-1 has recently been implicated as a mediator of gastric mucosal defense, an acceleration of the resolution phase of inflammation by ANXA-1 might prove to have therapeutic benefits. The possible role of ANXA-1 in gastric ulcer healing has not been described; therefore, we hypothesized that: 1) ANXA-1 protein expression along the ulcer margin will be increased during the healing of gastric ulcers; 2) The administration of the ANXA-1 peptide mimetic (Ac2-26) will accelerate gastric ulcer healing; 3) ANXA-1 -/- mice will exhibit impaired healing to NSAID-induced gastric damage. Methods: C57Bl6J mice (25-28 g) were anesthetized with halothane, opened with a midline laparotomy, and the stomach isolated. 200 µl of 20 % glacial acetic acid (GAA) was applied to the serosal side of the gastric antrum for 1 minute constrained within the barrel of a modified 1 ml syringe top. Total surface area at the time of induction = 28.2 mm2. Endpoints: Initial studies looked at both the changes in ulcer surface area (using planimetry), and the time course of ANXA-1 protein expression (by Western blot analysis) during the healing of gastric ulcers. The next set of experiments examined the effects of Ac2-26, Boc2 (ANXA-1 receptor antagonist, FPRL-1 selective), and dexamethasone, on gastric ulcer healing. Finally, we investigated whether ANXA-1 -/- mice were susceptible to NSAID-induced gastric damage. For these studies, indomethacin was administered by oral gavage, and then gastric damage scores were assessed at 5 and 24 hrs. Results: ANXA-1 protein was increased during the healing phase in the gastric ulcer margin: normal = 70 ± 11.7 INT/mm2; ulcer day 2, 121 ± 9.8; day 3, 115 ± 14; day 5, 109 ± 7.8, day 7, 127.3; day 10, 120 ± 10.4 (P < 0.05). In addition, Ac2-26 treatment significantly increased gastric ulcer healing whilst the ANXA-1 receptor antagonist Boc2, impaired the early phase of ulcer healing (P < 0.05). Finally, the ANXA-1 -/- mice were more susceptible to NSAID-induced gastric damage (P < 0.05 at 24 hrs post-indomethacin). Though early in the exploratory phase, these data support ANXA-1 as an endogenous anti-inflammatory mediator involved in the healing of damaged gastric mucosa.