Rats were either fed a 12% fat diet for 3 weeks, or rendered obese by administration of a 40 % fat diet for 6 months. In both cases, the rate of insulin secretion evoked by glucose in incubated pieces of pancreatic tissue was lower than that observed in tissue from control animals fed diets containing only 3 to 4 % fat. This reduction in the insulin secretory response to glucose occured despite the maintenance of a normal pancreatic insulin content. In the obese rats, the sensitivity to insulin of adipose tissue and muscle was also reduced. Thus, in these animals fed high-fat diets, obesity and peripheral insensitivity to insulin were not accompanied by a concomitant increase in the secretory response of the beta-cell to glucose, as seen in other types of experimental obesity. 1 This work was supported in part by grants-in-aid from the Lilly Research Laboratories (Indianapolis, Ind.) and the Upjohn Company (Kalamazoo, Mich.), and by the association contract Euratom-Universities of Pisa and Brussels (026-63-04 BIAC).