This study was undertaken to investigate the role of apoptosis in the integrity of blood-brain barrier (BBB) in subarachnoid hemorrhage (SAH). BBB permeability changes were examined and found increased on day 7 in a double hemorrhage rat model using Evans blue dye. The BBB permeability increase is coincidental to brain microvascular endothelial cell apoptosis (expression of caspase-8 and -9) occurring on Day 7. However, caspase-8 and caspase-9 inhibitors failed to protect the BBB. Considering that treatment did not completely inhibit apoptosis in brain microvascular endothelial cells, higher doses, earlier and/or multiple applications, and, possibly, more potent caspase inhibitors may be needed.