To determine the set of structural and functional changes in pancreatic islets (PI) of obesity-induced insulin resistant (IR) rats of different age (young and old) fed with prolonged (6 month) high-fat diet (HFD)(58% of fat) and further treatment with N-Stearoylethanolamine (NSE), a bioactive N-Acylethanolamine. Alimentary obesity-induced IR model in rats of two age groups was used to investigate the influence of age and NSE treatment on pancreas morphology (using histological, histochemical and immunohistochemical techniques) and on several biochemical parameters associated with DM onset. The NSE administration normalized pancreas morphology which was more affected in the old IR group; the signs of inflammation, edema, fibrosis and steatosis were somehow diminished and PI area became significantly increased. The amount of the AF-positive insulocytes increased and TUNEL-positive–decreased. Compensatory hyperplasia in the affected pancreas of both age was an important indicator of NSE stimulating effect. Protective effects of NSE on morpho-functional state of pancreas in HFD-induced IR rats of both age are associated not only with its anti-inflammatory, anti-oxidant and anti-dyslipidemic properties but also with activation of PI hyperplasia and β-cells compensatory mechanisms.