Silica nanoparticles (SiNPs) play a vital role in medicine applications such as drug delivery and cancer therapy.SiNPs can translocate into bloodstream through all possible routes of entry.However, there is scarce study on pre-thrombotic effect of SiNPs and mechanism of pre-thrombotic state in vivo.We specifically focused on the changes of platelets function and blood coagulationin Wistar rats after consecutive 7 days intravenous injectionof SiNPs (52 nm).The platelets aggregation assay, structural changes of platelets membrane glucoproteins, coagulation test, coagulant/anti-coagulant and fibrinolytic factors and the possible molecular mechanism of pre-thrombotic state formation were performed.Our results demonstrated a significant increase in platelets aggregation rate and platelet activation after SiNPs exposure.Clotting time were significantly shortened while fibrinogen (FIB) content was increased.There were sustained increases in coagulation factors and thrombin-antithrombin complex (TAT) expression induced by SiNPs.Antithrombin Ⅲ (AT-Ⅲ) of the SiNPs-treated groups were significantly decreased while concentrations of Tissue factor pathway inhibitor(TFPI), tissue plasminogen activator (t-PA)and D-dimer were elevated.The phosphorylation of nuclear factor-κB/p65 (NF-κB/p65) and activator protein-1/c-Jun (AP-1/c-Jun) and the protein levels of JNK were increased after SiNPs exposure.In summary, our results supported that SiNPscould induce the hypercoagulable and pre-thrombotic state in rats through the interaction between platelets activation, coagulation system hyperfunction and fibrinolytic system resistance.JNK-NF-κB/AP-1 pathway might be involved in regulation of pre-thrombotic state formation.