There is evidence that adipose tissue (AT) secretome affects the metabolic homeostasis, but little is known on adipocytokines (ACs) expression in the peri-pancreatic AT (PPAT) and their possible effects on the endocrine pancreas. We studied PPAT obtained from non-diabetic (ND) and T2D organ donors, and correlated ACs expression with donors’ clinical parameters and ex-vivo islet function. Protein lysates were prepared from frozen PPAT of 12 ND and 15 T2D, comparable for age (years) and BMI (kg/m2). By Luminex technology, a premixed 10-analytes panel (comprising Adiponectin/Acrp30, CCL2/JE/MCP1, C-Reactive Protein/CRP, Complement Factor D/Adipsin, IL-6, IL-10, Leptin, Resistin, Serpin E1/PAI-1, TNF-α) was selected for magnetic bead-based multiplex assay. Values of analytes reading between ND and T2D, expressed as median fluorescence intensity – MFI, were compared. Insulin secretion in response to glucose (g), glibenclamide (glib) and arginine (arg) from islets prepared by collagenase digestion and density gradient purification from the same donors, was also measured. We found that CCL2/JE/MCP1 and Resistin were approximately 3-fold lower in T2D compared to ND, while Leptin expression was 2-fold higher in T2D (p<0.05). No significant difference was observed for the remaining ACs. No correlation was found between ACs expression and the clinical characteristics of the organ donors. As expected, islet insulin stimulation index (iISI) in response to g, glib and arg was significantly lower in T2D (all p<0.01 vs ND). Interestingly, CCL2/JE/MCP1 positively correlated with iISI in response to arg in ND+T2D islets (p<0.01, R2=0.55), and Resistin positively correlated with iISI in response to g in ND islets (p<0.05, R2=0.54). In conclusion, this study: 1) shows, for the first time, that there are differences in PPTA of T2D vs ND; 2) confirms that β-cell responsiveness to several secretagogues is reduced in T2D; 3) suggests that there could be correlations between PPTA features and β-cell function. Supported by PNRR- M4C2-I1.3 Project PE_00000019 -HEAL ITALIA -CUP I53C22001440006 – Spoke 8.