CLEC5A and CLEC2 belong to the c-type lectin family and highly express on macrophage and platelet, respectively. CLEC5A mediates dengue virus (DV)-induced NLRP3 inflammasome activation and proinflammatory cytokines production in the macrophage. The anti-CLEC5A antagonistic antibody-treatment rescue the DV-caused hemorrhage and mortality. DV also induces platelet activation, apoptosis, and IL-1b production. However, the mechanism of DV-activated platelet in dengue virus-induced endothelium leakage still unclear. Here, we report that platelet strongly promotes DV-induced NET formation. DV-activated platelet release microparticles (MPs) to enhance NETosis. In addition, anti-CLEC2 blocking antibody inhibits the DV-induced CD62p expression of the platelet. Strikingly, we observed that DV activates platelet via CLEC2 to promote neutrophil undergo NETosis. Furthermore, DV stimulates platelet to release microparticles (MPs) to promote NET formation via CLEC2. Moreover, DV induces neutrophil extracellular traps (NETs) via CLE5A. Blockade both of CLEC5A and CLEC2 prevent DV-activated platelets and DVPMPs - initiated NETosis. In permeability assay, DPMPs-induced stronger endothelium leakage than DV, we also observed that block of CLEC2 prevents the DVPMPs-induced permeability change. Collectively, our observations suggest that CLECC2 and CLEC5A regulate the DV-induced NETs, CLEC2 also play a critical role in DV-induced endothelium permeability change.