Aim To explore the preventive effect and potential mechanism of β-blockers in vascular aging of spontaneously hypertensive rat (SHR). Methods 24 three-month-old male spontaneously hypertensive rats were randomly divided into placebo group, nifedipine group, nifedipine＋metoprolol group and metoprolol group, treated with edible starch, 60 mg nifedipine sustained-release tablets, 40 mg nifedipine sustained-release tablets＋75 mg metoprolol sustained-release tablets and 150 mg metoprolol sustained-release tablets, respectively. The rats fed with common diets for 9 months, and the blood pressure, heart rate and other general condition of the rats were dynamically measured. HE staining was used to observe the morphological characteristics of femoral aorta in rats. The vasomotor function of isolated femoral artery was tested by circumferential perfusion, immunofluorescence histological staining and real-time polymerase chain reaction (RT-PCR) were used to determine the expression of aging related genes p53 and p21, as well as endoplasmic reticulum stress related genes CHOP and XBP1. Results Compared with placebo group, systolic blood pressure decreased by about 30%, diastolic blood pressure decreased by about 20%, and heart rate decreased by 9%, 36% and 41% (all P＜0.01) in nifedipine group, nifedipine＋metoprolol group and metoprolol group, respectively. Compared with placebo group, the systolic and diastolic functions of nifedipine group, nifedipine＋metoprolol group and metoprolol group were significantly improved and the intima-media thickness decreased by 24%, 14% and 37% (all P＜0.01), respectively. Compared with nifedipine group and nifedipine＋metoprolol group, the systolic and diastolic functions of metoprolol group were significantly improved and the intima-media thickness decreased by 18% and 27% (all P＜0.01), respectively. Compared with the placebo group, the expression levels of p53 protein, p53 mRNA, p21 protein, p21 mRNA, CHOP protein, CHOP mRNA, XBP1 protein and XBP1 mRNA in nifedipine group decreased by 35% (P＜0.01), 23% (P＜0.05), 25% (P＜0.01), 3% (P＞0.05), 51% (P＜0.01), 24% (P＞0.05), 21% (P＜0.01) and 23% (P＞0.05), the nifedipine＋metoprolol group decreased by 36% (P＜0.01), 42% (P＜0.01), 4% (P＞0.05), 24% (P＜0.05), 32% (P＜0.01), 44% (P＜0.05), 13% (P＜0.01) and 42% (P＜0.05), the metoprolol group decreased by 47% (P＜0.01), 43% (P＜0.01), 42% (P＜0.01), 49% (P＜0.01), 78% (P＜0.01), 56% (P＜0.01), 32% (P＜0.01) and 81% (P＜0.01). Compared with nifedipine group and nifedipine＋metoprolol group, metoprolol group further inhibited the expression of genes related to aging and endoplasmic reticulum stress. Conclusions The arteries of spontaneously hypertensive rats show significant aging. β-blockers are better than calcium channel blockers in inhibiting vascular aging of spontaneously hypertensive rats, and at high doses β-blockers improve the degree of vascular aging better than combination therapy, and their mechanism may be related to the inhibition of endoplasmic reticulum stress.