Our previous studies indicated an increase in extracellularγ-aminobutyric acid (GABA) in rodent’s ischemic brain after Piroxicam administration, leading to alleviation of glutamate me-diated excitotoxicity through activation of type A GABA receptor (GABAA). This study was to investigate if GABAA activation by Piroxicam affects extracellular 5-hydroxytryptamine or not. High performance liquid chromatography revealed that there was a signiifcant decrease in ex-tracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum in Piroxicam pre-treated rat brains. This suggests a probable role of Piroxicam in reducing extracellular 5-hy-droxytryptamine release in ischemic cerebral cortex and striatum possibly due to the GABAA activation by Piroxicam.