Neuropeptide Y (NPY) concentration was determined by radioimmunoassay in selected hypothalamic regions microdissected from fresh brain slices of different types of diabetic rats. In spontaneously diabetic (BB) rats and streptozotocin (STZ)-induced diabetic rats, models of insulin-dependent diabetes mellitus, an elevated concentration of NPY was detected in the paraventricular nucleus (PVN) and arcuate nucleus (ARH) of the hypothalamus. In Wistar fatty rats, a model of non-insulin-dependent diabetes mellitus, NPY concentration was also high in the PVN as compared to controls. When STZ-induced diabetic rats were treated with insulin, elevated NPY content in the PVN returned to the normal level. These findings, together with our previous finding of increased secretion of insulin after microinjection of NPY into the PVN, suggest a crucial role of NPYergic neuronal system in the ARH-PVN area in controlling endocrine pancreas and glucose homeostasis.