Toll-like receptor 4 (TLR4) and cellular Src (c-Src) are closely associated with inflammatory cytokines and oxidative stress in hypertension,so we designed this study to explore the exact role of c-Src in the mechanism of action of the TLR4 signaling pathway in salt-induced hypertension.Salt-sensitive rats were given a high salt diet for 10 weeks to induce hypertension.This resulted in higher levels of TLR4,activated c-Src,pro-inflammatory cytokines,oxidative stress,and arerial pressure.Infusion of a TLR4 blocker into the hypothalamic paraventricular nucleus (PVN) decreased the activated c-Src,while microinjection of a c-Src inhibitor attenuated the PVN levels of nuclear factor-kappa B,pro-inflammatory cytokines,and oxidative stress.Our findings suggest that a longterm high-salt diet increases TLR4 expression in the PVN and this promotes the activation of c-Src,which upregulates the expression of pro-inflammatory cytokines and results in the overproduction of reactive oxygen species.Therefore,inhibiting central c-Src activity may be a new target for treating hypertension.