Thrombosis and its complications are a clinical condition that endangers health. Neutrophil extracellular trap networks (NET) are extracellular fibrous networks formed by neutrophil-released, depolymerized chromatin that influence disease regression by activating platelets, accelerating clotting and thus promoting thrombosis. Histidine decarboxylase (HDC), a key enzyme catalyzing histamine production, is highly expressed in neutrophils, particular in the bone marrow-derived immature myeloid cells. Histamine signaling is involved in allergic reactions, gastric acid secretion, inflammation, immune responses, and tumorigenesis in relation to a variety of physiological and pathophysiological events. Targeting HDC-expressing neutrophils and the regulation of histamine related downstream signal on neutrophil differentiation, NET formation and thrombogenesis development might become a new antithrombotic strategy. This article mainly reviews the role of HDC-expression neutrophils inthrombosis.