Clinical studies have indicated a frequent coexistence of depression and diabetes. Both of these diseases are associated with similar changes in the structure and function of the central nervous system cells and with similar disturbances of cognitive processes. Some morphological and functional changes occurring in these diseases seem to result from exaggerated glucocorticoid, proinflammatory cytokine or glutamate action. Glucocorticoids induced by stress are known not only to affect synaptic plasticity but also to disturb brain glucose metabolism and decrease insulin sensitivity. Functional neuroimaging studies demonstrated altered glucose metabolism in the brains of depressed patients. Changes in the amount or activity of key metabolic enzymes and a lower sensitivity of insulin receptors have been detected in the brains of animal models of both of these diseases. Hence, excess glucocorticoids can lead to impaired insulin action and glucose metabolism, to limited energy supply for proper neuronal function and, consequently, to disturbed synaptic plasticity.