Introduction: Peptic ulcer occurs due to an imbalance between factors that attack gastric mucosa and those protecting from damage. Phoenixin (PNX), a newly discovered peptide with PNX-14 and PNX-20 isoforms, is widely expressed in the brain and gastrointestinal tract(1,2). Apart from its role in reproductive functions and the regulation of food intake, it is considered as a regulatory peptide of the gut-brain axis(3). The aim of the study was to investigate the possible antiulcer efficacy of PNX-14. Methods: Ethical approval was obtained from Marmara University Animal Care and Use Committee (59.2020.mar). Female Sprague Dawley rats were randomised into “treatment plus pre-treatment” and “treatment without pre-treatment” groups.  In the pre-treated ulcer groups (n=16), PNX-14 (50 µg.kg-1.day-1) or saline was injected intraperitoneally for 3 days prior to ulcer induction. On the 4th day, under ketamine and chlorpromazine anaesthesia (100 and 10 mg.kg-1, intraperitoneally) acetic acid (80%, v/v) was applied for 1 min on serosal surface of stomachs, while control rats (n=8) had sham-surgery. Post-surgically, PNX-14 or saline treatment was continued for 3 consecutive days. In the “treatment without pre-treatment” groups (n=16), PNX-14 (50 µg.kg-1.day-1) or saline was administered for 3 days only after the ulcer-inducing surgery, and control rats (n=8) were treated with saline for 3 days following sham-surgery. On post-operative 3rd day, gastric serosal blood flow was measured under anaesthesia via laser Doppler flowmetry, and rats were then euthanised by exsanguination via cardiac puncture. Gastric levels of malondialdehyde (indicating lipid peroxidation), antioxidant glutathione and myeloperoxidase activity (indicating neutrophil infiltration) were measured by spectrophotometric methods. Gastric samples were stained by haematoxylin-eosin (injury scoring), toluidine blue (mast cells) and periodic acid Schiff (PAS; mucus-secreting cells and mucous secretion). Using GraphPad Prism 9.0 software, statistical analyses were made by one-way ANOVA and Student’s t-tests and expressed as mean ± SEM. Results: In saline-treated ulcer groups, gastric MPO activity (p<0.05-0.01), malondialdehyde levels (p<0.01-0.001) and microscopic damage scores (p<0.001) were elevated with respect to control groups, while gastric glutathione levels were reduced (p<0.01). The number of mast cells in submucosal and muscular layers were increased and PAS-positive surface /neck mucous cells were severely depleted in saline-treated ulcer groups. PNX-14 had no effect on myeloperoxidase activity, but PNX-14 given either as treatment or treatment plus pre-treatment reduced malondialdehyde levels (p<0.05) and histological damage scores (p<0.05), while depletion in gastric glutathione was abolished in PNX-pre-treated ulcer group (p<0.05).  Both modalities of treatments depressed the numbers of mast cells and increased the counts of PAS-positive cells. Gastric blood flow, which was not significantly altered in saline-treated ulcer groups, was decreased with PNX-14, reaching to statistical significance with its prolonged administration (p<0.05). Conclusions: Despite its inhibitory action on gastric blood flow, PNX-14 alleviated gastric mucosal damage by supporting mucosal defence through the maintenance of mucus layer and by reducing mast cell infiltration, but had no impact on neutrophil-mediated inflammation.