The antiphospholipid syndrome (APS) is characterized by venous or arterial thrombosis, and associated with dysfunctions of endothelial cells and monocytes. β2-glycoprotein I is a phospholipid-binding glycoprotein, and its antibodies have been reported to correlate strongly with thrombotic risk and play putative role in the pathogenesis of APS, whereas the biofunctions of anti-β2-glycoprotein I antibodies remain largely uncertain. It is noted that β2-glycoprotein I exhibits direct interaction with membrane Toll-like receptors, and through this interaction, the complex of β2-glycoprotein I and its antibodies induces intracellular signals via Toll-like receptors, resulting in activation of endothelial cells and monocytes, and expression of proinflammatory cytokines. In this review, we further discussed the recent findings of β2-glycoprotein I/antibody complex. Once activated by β2-glycoprotein I/antibody and their signals, endothelial cells release microparticle/extracellular vesicles which can further stimulate the surrounding rest cells with procoagulant and pro-inflammatory properties in a paracrine or/and autocrine manner. Novel evidence of β2-glycoprotein I/antibody complex bioactivities may provide insight into the molecular mechanisms that the complex regulates cell function and involves in APS pathogenesis.