The pancreatic somatostatin content in streptozotocin-induced diabetic rats was examined with or without insulin administration. Streptozotocin, 65 mg/kg, was injected into Sprague-Dawley rats via the tail vein. The control rats were given 0.1 M citrate buffer, pH 4.5. Half of the diabetic rats received saline injection and the other half were injected daily with 4 units of Lente Insulin (Novo) subcutaneously for 4 weeks. On the day after the last injection, the rats were sacrificed by decapitation. Trunk blood was collected and the blood glucose was determined with an autoanalyzer. The pancreas was quickly removed, and somatostatin and insulin were extracted with chilled 2N acetic acid. The material was centrifuged and the supernatant was lyophilized and assayed by radioimmunoassay. The somatostatin content of the pancreas and of isolated islets was increased in the diabetic rats, and the increased somatostatin content returned to the control level after insulin administration. The insulin content of the pancreas was decreased in the diabetic rats, and insulin administration did not alter the content. Blood glucose decreased in the diabetic rats treated with insulin. Body weight increased in the insulin treated rats, but did not increase in the non-treated diabetic rats. It is suggested that the effect of the insulin administration on the pancreatic somatostatin content might derive from improvement of the diabetic state and/or of the hyperglucagonemia and/or of the hypoinsulinemia.