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Anti-β2 glycoprotein Ⅰ (anti-β2GPI) antibodies are important contributors to the development of thrombosis.Anti-β2GPI antibody complexes with β2GPI are well known to activate monocytes and endothelial cells via the intracellular NF-κB pathway with prothrombotic implications.By contrast,the interaction of antiβ2GPI/β2GPI complexes with platelets has not been extensively studied.The p38 mitogen-activated protein kinase (MAPK) pathway has been recognized to be an important intracellular signaling pathway in the coagulation cascade and an integral component of arterial and venous thrombosis.The present study reveals that levels of antiβ2GPI/β2GPI complexes in sera are positively associated with p38MAPK phosphorylation of platelets in thrombotic patients.Furthermore,SB203580 inhibits anti-β2GPI/β2GPI complex-induced platelet activation.Thrombus formation decreased in p38MAPK/-mice after treatment with anti-β2GPI/β2GPI complexes.In conclusion,p38MAPK may be a treatment target for anti-β2GPI antibody-associated thrombotic events.