This work was conducted to investigate the effect of glimepiride on the brain chemical neurotransmitters norepinephrine (NE), serotonine (5- HT), gamma-aminobutyric acid (GABA) and dopamine (DA) in different brain areas namely cerebral cortex (C.C.), thalamus/ hypothalamus (TH), midbrain (M.B.) and cerebellum (C.) in streptozotocin (STZ) induced diabetes and to study the effect of Vit E separately and concomitantly with glimepiride on the previous neurotransmitters. .-. •• In diabetes induced experimentally in rats by streptozotocin (STZ) (50 mg/kg I.P) results of the present work showed significant elevation of NE level (P < 0.05) in CC, TH, and GABA in all tested brain areas and significant reduction of DA and 5HT levels (P0.05) of GABA, DA, NE and 5HT levels (P > 0.05) in all tested brain areas compared with diabetic non treated rats. Concomitant administrations of glimepiride (0.1 mg/kg orally) and Vit. E (0.1 mg/kg orally) showed significant reduction of GABA, significant elevation of 5HT levels (PO.05) in' all tested brain areas with significant reduction of NE level (PO.05) in CC, TH.