Objective:This study aims to investigate the effect of PI3K/Akt pathway on the regulation of large conductance Ca2+-activated K+ channel(BK channel)in diabetic coronary smooth muscle cells. Methods: Human coronary artery smooth muscle cells(HCASMC) were incubated with different concentrations of glucose(5 mmol/Land 15 mmol/L),reactive oxygen species(ROS) inhibitor GKT137831 and PI3K inhibitor wortmannin. Streptozotocin-induced diabetic rats were established successfully by intraperitoneal injection. Expression of DNA-Pkcs,Akt,p-Akt(S473), BK-α subunit and BK-β1 subunits were determined by Western blot. ROS generation in HCASMC was measured in terms of fluorescence using the cell-permeable fluorogenic probe DCFH-DA. Results: Compared with that of HCASMC incubated in 5 mmon/L glucose concentration,the expression of DNA-Pkcs,Akt,p-Akt(S473) increased significantly and BK-β1 subunit decreased significantly(P < 0.05). Compared with the control group,the expression of p-Akt(s473)decreased significantly(P < 0.05) and BK-β1 increased significantly (P < 0.05) after pretreated with Wortmannin. Conclusion:PI3K/Akt channel is involved in the regulation of BK channel expression in diabetic coronary smooth muscle cells.