The main findings of the present study are: (1) High salt treatment led to endothelial dysfunction in C57BL/6 mice, in isolated thoracic aortic rings from C57BL/6 mice, and in MAECs; (2) high salt-induced endothelial dysfunction was alleviated in NALP3-/- mice and in MAECs by either down-regulating NALP3 or decomposing H2O2; (3) high salt increased NALP3 expression in MAECs and inhibiting NALP3 reversed the down-regulated expression of p-eNOS induced by high salt in MAECs. The gene discussed is NLRP3; the disease is endothelial dysfunction.