In hypertensive patients, increased oxidative stress is thought to be one important cause of vascular dysfunction. Recently, it has been suggested that hydrogen exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radical and peroxynitrite, the most cytotoxic chemicals of reactive oxygen species (ROS). Herein, we investigated the protective effect of chronic treatment with hydrogen-rich saline (HRS) against vascular dysfunction in SHR and the underlying mechanism. The 8-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY) were randomized into HRS-treated (6 ml/kg/day for 3 months, i.p.) and vehicle treated group. Treatment with HRS ameliorated vascular dysfunction including aortic hypertrophy and endothelial function in SHR. Treatment with HRS had no significant effect on blood pressure, but it significantly improved baroreflex function in SHR. Treatment with HRS abated oxidative stress, restored antioxidant enzymes including superoxide dismutase, glutathione peroxidase, and catalase, and suppressed NADPH oxidase. Furthermore, treatment with HRS depressed pro-inflammatory cytokines expression including IL-6 and IL-1β and suppressed NF-κB activation, restored mitochondrial function including ATP formation and membrane integrity. In addition, although treatment with HRS had no significant effect on nitric oxide amount in circulating or aorta, it suppressed endothelial nitric oxide synthase expression and upregulated dimethylarginine dimethylaminohydrolase 2 expression in SHR. In conclusion, treatment with HRS alleviates vascular dysfunction through abating oxidative stress, restoring baroreflex function, suppressing inflammation, preserving mitochondrial function, and enhancing nitric oxide bioavailability.