Morus alba is being used in the prevention of diabetes mellitus. Our goals are to evaluate the precise mechanisms underlying neuroprotective effects of Egyptian M. alba against brain damage induced by diabetes in rats. Diabetes was induced by streptozotocin (STZ; 52 mg/kg; i.p). Rats were divided into five groups: normal group received saline, diabetic group, Glimepiride (0.5 mg/kg) and M. alba (250 & 500 mg/kg) groups. All treatments daily administered orally for a period of 10 days. STZ group increased serum glucose level, brain nitric oxide and malondialdehyde contents, decreased brain glutathione and B-cell lymphoma-2 contents, produced alteration in seretonine, norepinephrine and dopamine brain contents and showed many degenerating neurons and cell injury with caspase-3 expression. Whereas treatment with Morus alba corrected all biochemical and histopathological changes with inhibition of caspase-3 expression. In conclusion, Morus alba ameliorated neurologic complications induced by diabetes and considered as an anti-apoptotic and neuro-protective plant.