The cholecystokinin B receptor (CCKBR) is localized on pancreatic endocrine somatostatin δ-cells. Pancreatic somatostatin content was increased in diabetic rats. The mechanisms involved in this phenomenon are unknown, and we believe insulin is involved. In this study, four groups of rats were used: controls, streptozotocin-induced diabetic, streptozotocin-induced diabetic with insulin, and streptozotocin-induced diabetic with insulin and its cessation. Rats were killed after 7–28 days of treatment for diabetes, and somatostatin mRNA expression and pancreatic somatostatin content, CCKBR mRNA and protein expression evaluation in total pancreas and purified islets, and the cellular localization of somatostatin and CCKBR in islets was measured. Data indicate that diabetes is established after 7 days, is controlled by insulin, and reappears after treatment cessation. Pancreatic somatostatin mRNA expression and somatostatin content were increased during diabetes, normalized during insulin treatment, and reaugmented after treatment cessation. Gland and islet CCKBR mRNA and protein almost disappeared during diabetes; CCKB mRNA reappeared in response to insulin, but the protein did not. Confocal microscopy confirmed data obtained on somatostatin and CCKBR as established biochemically in the course of the treatments. In conclusion, these data strongly suggest that insulin can negatively control pancreatic somatostatin mRNA and hormone content and positively control CCKBR mRNA; the CCKBR protein appears to be delayed.