The excitatory amino acids (EAA) like glutamate, aspartate and inhibitory neurotransmitter GABA (gama amino butyric acid) play an important role in the pathophysiology of cerebral ischemia. The objective of the present study is to elucidate the role of endogenous GABA against EAA release in different regions during ischemia. The transient focal ischemia was induced in rats by using middle cerebral artery occlusion model (MCAo). The results indicate gradual elevation of brain glutamate, aspartate and GABA level at different brain regions and attained peak level at 72 h of ischemic reperfusion (IR). At 168 h of IR the EAA levels declined to base line but GABA level was found to be still elevated. The biochemical analysis shows the depleted brain ATP, Na+K+ATPase content and triphasic response of glutathione activity. It can be concluded that time dependent variation in the EAA and GABA release, endogenous GABA can be neuroprotective and earlier restoration of energy deprivation is essential to prevent further neurodegeneration. To have efficient treatment in ischemic condition, multiple approaches like energy supply, antagonism of EAA, controlling calcium function are essential.