alphaB-crystallin, a low-molecular-weight heat shock protein (HSP), has binding sites on platelets. However, the exact role of alphaB-crystallin is not clarified. In this study, we investigated the effect of alphaB-crystallin on platelet granule secretion. alphaB-crystallin attenuated the adenosine diphosphate (ADP)-induced phosphorylation of p44/p42 mitogen-activated protein kinase (MAPK) and p38 MAPK. The ADP-stimulated HSP27 phosphorylation was markedly reduced by alphaB-crystallin. alphaB-crystallin significantly suppressed the ADP-induced secretions of both platelet-derived growth factor (PDGF)-AB and serotonin. Therefore, our results strongly suggest that alphaB-crystallin extracellularly suppresses platelet granule secretion by inhibition of HSP27 phosphorylation via p44/p42 MAPK and p38 MAPK.