Phoenixin (PNX) is a neuropeptide, has a role in reproduction, food intake, energy balance behaviour, and response to stress. PNX immunostaining has been shown in periphery of islets of Langerhans(1).  It stimulates insulin secretion, promotes glycolysis, prevents gluconeogenesis (2,3), reduces inflammation and ROS formation in mice model of fatty liver (4).   Aim of the study to investigate in vivo effect of PNX on experimental rat model of diabetes induced by streptozotocin (STZ) and nicotinamide (NA) which causes oxidative stress in B cells of pancreatic islets.  Experimental protocols were approved by the Marmara University Animal Care and Use Committee. Male, 12 weeks old, Sprague-Dawley rats were injected PNX-14/vehicle in dosages of 0.45 and 45 nmol/kg intraperitoneally (ip) 7 day before and 8-9-10 days after induction of diabetes by NAD 110 mg/kg and STZ 65 mg/kg ip administration. Glucose tolerance were measured before STZ injection. Fasting blood glucose and, gastric emptying rate of methyl cellulose was measured at the last injection date. Rats were decapitated. Blood, pancreas, ileum and liver were harvested. Plasma insulin, testosteron, tissue myeloperoxidase activity (MPO), luminol and lucigenin enhanced chemiluminesance, tissue insulin mRNA was measured. Histological evaluation was done. Insulin immunoreactivity was expressed as percentage of total islet area in insulin immunolabeled slides.  Results were summarized in Table.1.  Table.1.Effects of PNX on blood glucose, gastric emptying rate and pancreas*   FBG mg/dL  % gastric emptying Luminol rlu/mg tissue Lucigenin rlu/mg tissue % area of Insulin IR cell NC (n=5) 77±6.7 52,6±17.2       15.3±1.9 21.8±10.5 34.8±17.3 N-PNX-0.45 n=6 74±9.8 49,1±10.52 27,4±4.99 16.0±3.2 54.0 ±6.8 N-PNX-45 n=6 73±15.8 53,3±8,99   21.4±6.4 19.4±5.2 66.4±6.8 DC n=6 189.9±124 68,1± 5.4     56.4±16.8 59.9±16.2 18.8±10.2 D-PNX-0.45 n=6 176.8±86.2 75,6±7.3  32.4 ± 13.2 33.5± 12.4 49.2 ± 11.8 D-PNX-45 n=5 139.8±66.2 68, ±14.45 29.3±11.1 34.8 ± 11.6 29.6 ± 7.7 Two-way ANOVA           Interaction 0.6 0.06 0.0001 0.0195 0.002 Diabetes 0.0004 0.0002 <0.0001 <0.0001 <0.0001 PNX 0.6 0.59 0.045 0.001 <0.0001 *mean± standart deviation, N, normal, D Diabetic, C saline PNX, Phoenixin IR, immunoreactive, FBG fasting blood glucose   PNX treatment increased insulin immunoreactive cells in pancreatic islets of normal rats.  It regenerated organization of pancreatic islets, reduced number of degenerated cells in diabetic rats, increased percent area of insulin immunoreactive cells.  PNX reduced oxidative injury in pancreas without altering MPO activity.  PNX lowered fasting blood glucose at the end of experiment even in the presence of increased blood testosteron level. Plasma insulin level and expression of insulin mRNA in pancreas was not changed by PNX.  Gastric emptying rate of semisolid meal decreased only in nondiabetic rats treated with PNX.  Our findings suggest that PNX reduces pancreatic injury and lowers blood glucose in advance by reducing oxidative burden. Further studies are needed to clarify if PNX may be an attractive alternative in the treatment of diabetes.