Hyperglycemia　and　hypertension　are　considered　to　be　the　two　leading　risk　factors　for　vascular　disease　in　diabetic　patients.　However,　few　pharmacologic　agents　could　provide　a　combinational　therapy　for　controlling　hyperglycemia　and　hypertension　at　the　same　time　in　diabetes.　The　objectives　of　this　study　are　to　investigate　whether　berberine　treatment　could　directly　reduce　blood　pressure　and　identify　the　molecular　mechanism　underlying　the　vascular　protection　of　berberine　in　diabetic　rats.　Berberine　was　intragastrically　administered　with　different　dosages　of　50,　100　and　200　mg/kg/day　to　diabetic　rats　for　8　weeks　since　the　injection　of　streptozotocin.　The　endothelium-dependent/-independent　relaxation　in　middle　cerebral　arteries　was　investigated.　The　activity　of　large-conductance　Ca2+-activated　K+　channel　(BKCa)　was　investigated　by　recording　whole-cell　currents,　analyzing　single-channel　activities　and　assessing　the　expressions　of　a-and　beta　1-subunit　at　protein　or　mRNA　levels.　Results　of　the　study　suggest　that　chronic　administration　of　100　mg/kg/day　berberine　not　only　lowered　blood　glucose　but　also　reduced　blood　pressure　and　improved　vasodilation　in　diabetic　rats.　Furthermore,　berberine　markedly　increased　the　function　and　expression　of　BKCa　beta　1-subunit　in　cerebral　vascular　smooth　muscle　cells　(VSMCs)　isolated　from　diabetic　rats　or　when　exposed　to　hyperglycemia　condition.　The　present　study　provided　initial　evidences　that　berberine　reduced　blood　pressure　and　improved　vasodilation　in　diabetic　rats　by　activation　of　BKCa　channel　in　VSMCs,　which　suggested　that　berberine　might　provide　a　combinational　therapy　for　controlling　hyperglycemia　and　blood　pressure　in　diabetes.　Furthermore,　our　work　indicated　that　activation　of　BKCa　channel　might　be　the　underlying　mechanism　responsible　for　the　vascular　protection　of　berberine　in　diabetes.