Aging is associated with insulin resistance, but the exact molecular mechanism is unknown. Tumor Necrosis Factor a (TNF-a), Interleukin 6 (IL-6) and other pro- or anti- inflammatory cytokines appear to participate in the induction and maintenance of the sub acute inflammatory state associated to aging. Furthermore, it has been shown that pancreatic islet endocrine cells may be a source of cytokines and other pro-inflammatory mediators during different pathological conditions. However, little is known about the effect of aging on these cells. The aim of the present study was to investigate the effect of aging on different cytokines related to inflammation in the pancreas of 2- and 12-month-old SAM-P8 mice. Insulin content of the pancreas and insulin release were also examined. Glucose was measured as a metabolic control of insulin action. Insulin was measured by radioimmunoassay, and cytokines assays were performed using specific enzyme-linked immunoabsorbent assay kits. Aging significantly increased plasma insulin levels, while insulin content of the pancreas was significantly decreased in old mice, suggesting age-related alteration in both, insulin action and synthesis. The level of pro-inflammatory cytokines like TNFa, Interleukin 1b, IL-6 and Interleukin 2 (IL-2) were significantly increased in the pancreas of old mice (p<0.01), whereas the anti-inflammatory interleukin 10 (IL-10) showed a decrease during aging (p<0.05) suggesting a possible role for cytokines produced by the pancreas in regulating b cell function. We can speculate that pancreas may play an active role in modulating local response by elaborating proinflammatory molecules. Acknowledgment: RETICEF- RD06/0013 and SAF2007 66878-C02–01