The clinical impact of severe hypoglycemic brain insult is ranged from alterations of mental status to profound coma and death. However, the exact mechanism of hypoglycemic brain insult is not well known yet. We report a case of a 75-year-old female with diabetes, who developed dementia after a severe hypoglycemic event. Diffusion-weighted magnetic resonance imaging detected an increased signal intensity in the splenium of corpus callosum. After 6 days, follow-up MRI (T2 weighted imaging) revealed irreversible signal abnormalities in the splenium of corpus callosum. Also, SPECT (Single Positron Emission Computed Tomography) and PET (Positron Emission Tomography) revealed decreased cerebral functions in left parietal, temporal and occipital lobes. This case brings up better understanding for the extent and mechanism of hypoglycemic brain insult.