Abstract: Epileptic seizures are one of the most common neurologic disorder and lead to disruption of Blood-brain Barrier (BBB). In animal experiments, seizure susceptibility has been shown to increase with incremental blood glucose. Moreover, clinical information regarding seizures and parameters of glucose control is lacking. The aim of this study is to examine the effect of acute hyperglycemia on permeability of Blood Brain Barrier (BBB) and the immunoreactivity of Zonula occludens-1 (ZO-1) and Glial Fibrillary Acidic Protein (GFAP) during Pentylenetetrazole (PTZ)-induced epileptic seizures. Experimental rats are divided into four groups. Evans blue was used as BBB tracer; ZO-1 and GFAP were determined by an immunohistochemical method. The BBB permeability of three parts of the brain in acute hyperglycemia+PTZ group compared to PTZ group (p<0.05). Immunoreactivity of ZO-1 decreased in acute hyperglycemic rats (p<0.05). GFAP immunoreactivity also significantly increased in PTZ and acute hyperglycemia+PTZ (p<0.01). This study was conducted to determine if acute hyperglycemia aggravates seizure changes GFAP activation and increases BBB damage during seizures.