To investigate the pancreatic exocrine function in noninsulin-dependent diabetes mellitus (type 2 DM), we evaluated the pure pancreatic juice obtained by endoscopic cannulation of the main pancreatic duct in 13 healthy control subjects and 22 patients with type 2 DM who had no evidence of pancreatic disease. Samples of pancreatic juices were collected in six fractions for 30 minutes at 5-minute intervals after an intravenous bolus injection of secretin (0.25 CU/kg) and cholecystokinin-8 (CCK) (40 ng/kg). The responses of plasma glucose, insulin, and C-peptide to intravenous administration of glucose (50%, 40 mL) were measured. The levels of plasma insulin and C-peptide levels in type 2 DM were the same as in healthy controls in the basal state but did not further increase in response to an intravenous glucose. This suggested that patients with type 2 DM had insulin secretion defect rather than insulin deficiency. Pancreatic secretions including volume, bicarbonate, and protein output in response to stimulation with secretin, and CCK were significantly reduced when compared to the healthy controls. We conclude that patients with type 2 DM exhibit impairment of pancreatic exocrine secretion and that this impairment might not be related to insulin deficiency. Therefore, we recommended that careful evaluation for exocrine pancreatic function in type 2 diabetics who have any clinically suspicious symptoms of pancreatic insufficiency.