Animal studies have shown diabetes-induced changes in the state and function of the serotonin neuroreceptor system. Diabetes also has induced structural and functional alterations in hippocampus and been associated with altered hypothalamopituitary adrenal axis regulation. In this study, serotonin-1A (5-HT(1A)) receptor binding was measured in humans with type 2 diabetes (n=6) and healthy controls (n=6), using positron emission tomography (PET) and [carbonyl-11C]WAY 100635. Significantly greater 5-HT(1A) receptor binding was detected in mesial temporal cortex, including hippocampus (P<0.05) for type 2 subjects (relative to controls). Within the type 2 group, glycosylated hemoglobin and stressed plasma cortisol levels were positively correlated (P<0.02). These findings support previous studies that suggest serotonergic underpinnings to the neurobiology of diabetes and have shown diabetes-induced neurological changes in hippocampus.