Changes in plasma insulin levels in response to enteral administration of insulin have been studied in rabbits.Insulin, when administered to the stomach, did not cause hypoglycemia at doses up to 150 U./kg. When insulin at doses over 40 U,/kg. was infused to the upper jejunum via an indwelling catheter, there was a slight but significant increase in plasma insulin levels, followed by a significant fall in blood glucose. A considerable increase in plasma insulin was observed when insulin at doses over 20 U./kg. was infused to the Thiry-Vella loop of the jejunum in which no pancreatic secretion entered. With a dose of 100 U./kg., the mean plasma insulin rose promptly to the peak of 241 /tU./ml., followed by a severe hypoglycemia.As judged by hypoglycemic and immunological responses, insulin can be absorbed from the intestine in a physiologically active form, but the fraction absorbed is relatively small. DIABETES 21: 203-208, April, 1972. A number of recent investigations either in vitro by the use of everted sac technic 1 or in vivo, has indicated that insulin can be absorbed from the small intestine of mammals in the presence of dyes, 2 saponins, 3 water-inoil-in-water emulsions 4 or proteolytic inhibitors. 1 ' 5 " 7 As a result, it has been held that insulin is not irreversibly altered and at least part of the hypoglycemic activity might be restored.To the best of our knowledge, there has been no systematic comparison made of the effects of insulin administered via the gastrointestinal tract and the serum insulin levels. To obtain additional information on the