Introduction: Neuropeptide W (NPW) regulates food intake and energy homeostasis, and was recently shown to have anti-oxidant and anti-inflammatory effects1,2. The present study was aimed to investigate the possible beneficial effects of NPW treatment on colonic injury in rats induced with colitis. Methods: Following the ethical approval by Marmara University Animal Care and Use Committee (33.2020.mar), Sprague Dawley female rats were randomised to control (n=8) or colitis groups (n=30) treated with saline or NPW (0.5, 1 or 5 µg.kg-1.day-1). Under light ether anaesthesia, colitis was induced by intracolonic administration of 1 ml of 5% (v/v) acetic acid diluted in saline through a polyethylene tube, which was positioned in the colon 8 cm past the anus, while intracolonic saline was instilled in the control group. Saline or NPW was injected subcutaneously immediately after the administration of acetic acid, and the treatments were continued in the following 4 days. At the 24th h following the last treatment, colonic blood flow was monitored under ketamine and chlorpromazine (100 and 10 mg.kg-1, intraperitoneally) anaesthesia using a laser Doppler. Then, animals were decapitated and the distal 8 cm of the colon were removed for macroscopic scoring, determination of tissue wet-to-dry weight ratio and biochemical analyses. Colonic levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α were detected by commercial enzyme-linked immunosorbent assay (ELISA) kits, and malondialdehyde (MDA; showing lipid peroxidation), glutathione (GSH; antioxidant) and myeloperoxidase activity (MPO; indicator of neutrophil infiltration) levels in the colon were measured spectrophotometrically, while cyclooxygenase (COX) activity was determined by a fluorometric assay. COX-1 and COX-2 protein expressions were detected by western blotting. The statistical analyses of the data were carried out by one-way ANOVA using the GraphPad Prism 9.0 software. Results: No significant differences in food intake, body weight, stool weight or colonic levels of IL-6, TNF-α and COX-1 expression were present among the experimental groups. Macroscopic score, wet/dry weight ratio, MPO activity, MDA level and COX-2 expression levels were increased in the colonic tissues of saline-treated colitis rats as compared to control group (p<0.05–0.001), while blood flow, GSH level and COX activity were significantly lower than those of the control group (p<0.05–0.001). Colonic oedema was not reduced in NPW-treated groups, but macroscopic scores in NPW-treated (0.5 and 5 µg.kg-1) groups were not different than that of the control group. Colitis-induced elevation in MDA level was abolished with all 3 doses of NPW (p<0.01-0.001), but MPO activity was reduced only at its 5 µg.kg-1 dose of NPW (p<0.05). NPW, at the 5 µg.kg1 dose, also elevated colonic blood flow (p<0.05) and replenished the depleted glutathione level (p<0.05). In NPW-treated groups (0.5 and 5 µg.kg-1), colitis-induced elevation in COX-2 protein expression was abolished (p<0.001), but the depressed COX activity was not altered by NPW treatment. Conclusions: NPW ameliorated acetic acid-induced oxidative colonic injury in rats through the upregulation of colonic blood flow and the inhibition of COX-2 protein expression.