In man and in rat, the diabetic state is associated with diseases of exocrine pancreatic function. In this work, streptozotocin diabetes was shown to lead to a 95% decrease in the amylase to lipase ratio in rats. Diabetes was reversed by either pancreas transplantation or insulin treatment. Transplantation of neonatal pancreases was successful in reversing the diabetic-induced alterations of exocrine pancreatic function. To assess whether insulin acts directly on the exocrine pancreas, or through the enhancement of glucose utilization, animals were fed either a low-fat diet or a high-fat diet during insulin treatment; this latter diet is well known to impair insulin’s effect on glucose metabolism. When diabetic rats were fed a low-fat diet, insulin treatment was able to correct the hyperketonemia and to reverse the amylase to lipase ratio to the prediabetes level. In contrast, the insulin treatment failed to restore the amylase to lipase ratio when the diabetic rats were fed the high-fat diet. Despite insulin treatment, the hyperketonemia worsened implying that glucose utilization remained low as would be expected on a high-fat diet. The dependence of the insulin effect upon diet composition demonstrates that the rate of glucose metabolism is the primary factor in the regulation of amylase to lipase rati