Objective Large-conductance culcium-activated potassium (BKCa) channel modulates vascular smooth muscle tone. In the present study, we tested the hypothesis that salt, one of the factors which significantly influence bleed pressure (BP), can regulate BKCa activity and then elevate blood pressure. Methods Male Spragne-Dawley rats aged 6 weeks were randomized into high salt diet group (HS) and control group, fed with high salt diet (containing 5% NaCi) and standard rat chow (containing 0.4% NaCl) respectively for 16 weeks. Tail systolic blood pressure (SBP), body weight (BW) and 24-hour urinary output were tested every 4 weeks. Content of urinary Na+ was detected using flame spectrophotometrical method. At the end of 16 weeks, all the rats were killed, the mesenteric arteries were obtained, and single mesenteric smooth muscle cells were isolated at once. The resting membrane potential (Em), the total potassium currents and the currents after perfusion with TEA solution of the cells were all recorded by whole cell patch clamp. The transcriptions of BKCa channel α and β1 sobunits in mesenteric arterial vascular smooth muscle cells (VSMC) of each group were calculated by real-time RT-PCR. Results There was no difference in SBP and BW at each stage between control group and HS group; the urinary Na+ level in HS animals was elevated significantly after 4 weeks.The negative values of Em in HS group VSMCs were reduced compared with these in the control group. Transcriptions of β1 subanit of BKCa channels were decreased in HS group, but α subunit transcriptions did not differ between the two groups. Whole cell potassium currents did not differ hetween HS and control groups, but BKCa currents of HS group VSMCs were lower than these of control group ones. Conclusion Even without elevating SBP, salt-loading can still modulate the expression and activity of BKCa channel in the mesenteric arterial VSMC and elevate vascular tone.