In the present study dopamine was measured in the hypothalamus, brainstem, pancreatic islets and plasma, using HPLC. Dopamine D2 receptor changes in the hypothalamus, brainstem and pancreatic islets were studied using [3H] YM-09151–2 in streptozotocin-induced diabetic and insulin-treated diabetic rats. There was a significant decrease in dopamine content in the hypothalamus (P < 0.001), brainstem (P < 0.001), pancreatic islets (P < 0.001) and plasma (P < 0.001) in diabetic rats when compared to control. Scatchard analysis of [3H] YM-09151–2 in the hypothalamus of diabetic rats showed a significant decrease in Bmax (P < 0.001) and Kd, showing an increased affinity of D2 receptors when compared to control. Insulin treatment did not completely reverse the changes that occurred during diabetes. There was a significant decrease in Bmax (P < 0.01) with decreased affinity in the brainstem of diabetic rats. The islet membrane preparation of diabetic rats showed a significant decrease (P < 0.001) in the binding of [3H] YM-09151–2 with decreased Kd (P < 0.001) compared to control. The increase in affinity of D2 receptors in hypothalamus and pancreatic islets and the decreased affinity in brainstem were confirmed by competition analysis. Thus our results suggest that the decreased dopamine D2 receptor function in the hypothalamus, brainstem and pancreas affects insulin secretion in diabetic rats, which has immense clinical relevance to the management of diabetes.