Aim To explore the role of β1 submit promoter methylation when hypertension and aging regulate the activity of large-conductance Ca²＋-activated K＋ channel in mesenteric arteries. Methods Male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were studied at 3,6 months of age, blood pressure was noninvasively measured in the caudal artery, the mesenteric arteries were taken for the experiment. The whole-cell K＋ currents and BKCa single channel currents were measured using whole-cell and inside-out patch, respectively. Isometric contraction study was performed to investigate the contribution of BKCa channel to vascular tone regulation. Western blot was used to detect the expression of α and β1 submit of BKCa channel in mesenteric arteries. DNA bisulfite sequencing PCR was performed to investigate of the DNA methylation status at β1 gene (KCNMB1) promoter. Results At 3 months old, compared to WKY, the mean peak BKCa current density of SHR was significantly increased. Aging decreased the mean peak whole-cell current density of both SHR and WKY. The increases in the Po of BKCa channels that tamoxifen evoked in WKY were significantly lower than those of age-matched SHR. Meantime, hypertension increased the contribution of BKCa channels in vascular tone regulation. Compared with age-matched WKY, the protein expression level of the β1 subunit observed in SHR was always significantly increased. Aging reduced β1 subunit expression in mesenteric arteries. Hypertension decreased BKCa channel β1 submit promoter methylation in mesenteric arteries, in contrast, aging increased BKCa channel β1 submit promoter methylation in mesenteric arteries. Conclusions During hypertension, KCNMB1 gene demethylated and the expression of β1 submit increased, which enhanced the function of BKCa channel. Aging not only enhanced CpG methylation at KCNMB1 gene promoter but also upregulated β1 subunit expression, which diminished the function of BKCa channel.