Our major findings include: 1) cerebral ischemia induces a time-dependent increase of blood occludin levels during the first 4.5 hours after MCAO onset, with a sharp increase at 4.5-hour MCAO; 2) two major occludin fragments (55 kDa and 31 kDa) are identified in the blood during cerebral ischemia; 3) BBB damage occurs early after stroke onset with a massive leakage at 4.5-hour MCAO, and blood occludin levels increase proportionately to the magnitude of BBB damage; 4) blood occludin levels remains significantly higher than its basal level within the first 24 hours after MCAO onset. Here, OCLN is linked to brain ischemia.