Studies are presented dealing with the effect on the exocrine and endocrine pancreas of long-term oral trypsin inhibitor administration to alloxan diabetic rats. Three categories of rats were used: a) normal rats, b) alloxan diabetic rats, and c) alloxan diabetic rats treated with the trypsin inhibitor. 1. The concentration of amylase in both pancreas and intestinal contents were markedly decreased in alloxan diabetic rats as compared with normal rats, whereas the concentrations of lipase and trypsin(ogen) were practically unaffected by the diabetic state. 2. Trypsin inhibitor treatment of diabetic rats enhanced the concentrations of both amylase, trypsin(ogen), and lipase in pancreas and intestinal contents when compared with untreated diabetic controls. 3. Alloxan diabetic rats treated with trypsin inhibitor displayed an increased weight gain, increased pancreatic weight, and increased pancreatic protein concentration as compared with the untreated diabetic controls. 4. Alloxan diabetic rats treated for 3 or 5 weeks with the trypsin inhibitor were found to have decreased basal blood glucose levels and an increased plasma insulin: blood glucose ratio as compared to the untreated diabetic controls. 5. There was no apparent difference in the glucose elimination rate after I.V. glucose loads in diabetic rats given trypsin inhibitor and their diabetic controls. However, the insulin secretory response to the glucose stimulus was slightly improved in the trypsin inhibitor group. 6. Alloxan diabetic rats treated with trypsin inhibitor had an increased total pancreatic insulin content compared with their diabetic controls. It is concluded that long-term daily treatment with oral trypsin inhibitor in alloxan diabetic rats increased enzyme production and secretion in the exocrine pancreas, and produced an improvement of the diabetic condition of the animals. This improvement might partly be due to an increased pancreatic content and secretion of insulin.