Disuse and aging are associated with changes in glucose metabolism and insulin responsiveness of skeletal muscle. However, their combined effects on the islets of Langerhans in the pancreas and serum insulin levels have not been studied. The goal of this study was to investigate the response of the pancreas to disuse, induced by hind limb suspension (HS), in young and old animals. Male Fisher 344 X Brown Norway rats at 6 (young) and 32 (old) months of age were subjected to 14 days HS. Serum insulin and pancreas morphology were examined. Serum insulin concentration was lower in old rats, and decreased significantly following HS in young, but not old rats. Islets of Langerhans in the pancreas showed a more diffuse appearance in the old rats independent of HS, but no statistically significant differences were observed in islet area, cells per islet, or area occupied by islets. However, in old animals, but not young, HS was associated with an increase in islet number. No differences were observed in the percentage or area of insulin positive cells in the pancreas. We conclude that the insulin secretion response to disuse is lost at old age, and this can not be explained by changes in islet size or insulin positive cell number. The implications of changed appearance and number of islets in old rats in response to HS remain to be investigated.