Concentrations of monoamines and their metabolites were investigated in various brain regions of 3, 50, and 100 days diabetic mice. An increase in the content of norepinephrine was observed in the pons-medulla and striatum in short-term (3 days) diabetic mice, and could be sustained for 100 days and 50 days, respectively. In the hypothalamus and cortex, the increase of norepinephrine was observed in both 50 and 100 day diabetic mice, but that of cerebellum was only observed in the 100 day diabetic mice. The concentration of dopamine was increased in the striatum both in short-term and long-term (50 and 100 days) diabetic mice, that of pons-medulla and cortex was increased in the long-term diabetic mice. Concentrations of the acidic metabolites of dopamine, dihydroxyphenylacetic acid and homovanillic acid were decreased in the hypothalamus, hippocampus and striatum, while increased in the pons-medulla and cortex. 5-Hydroxytryptamine concentration was increased in the hypothalamus, hippocampus, pons-medulla and cortex progressively from short-term to long-term diabetic mice. However, the concentration of its acidic metabolite, 5-hydroxyindoleacetic acid, was decreased in the hypothalamus, hippocampus, striatum, pons-medulla and cortex. These data suggest that diabetes is associated with a significant disturbance of brain monoamine metabolism. This disturbance was not generalized but related to some specific areas of the brain and some of these alterations were progressive from short term to long term diabetes.