Background Increased risk of bladder cancer has been reported in diabetic patients.This study was to investigate the roles of mitogen-activated protein kinase kinase (MEK) 1 and 2 in the regulation of human insulin-and insulin glargine-induced proliferation of human bladder cancer T24 cells.Methods In the absence or presence of a selective inhibitor for MEK1 (PD98059) or a specific siRNA for MEK2 (siMEK2),with or without addition of insulin or glargine,T24 cell proliferation was evaluated by cell counting kit (CCK)-8 assay.Protein expression of MEK2,phosphorylation of ERK1/2 and Akt was analyzed by West blotting.Results T24 cell proliferation was promoted by PD98059 at 5-20 μmol/L,inhibited by siMEK2 at 25-100 nmol/L.PD98059 and siMEK2 remarkably reduced phosphorylated ERK1/2.Insulin-and glargine-induced T24 cell proliferation was enhanced by PD98059,suppressed while not blocked by siMEK2.Insulin-and glargine-induced ERK1/2 activation was blocked by PD98059 or siMEK2 treatment,whereas activation of Akt was not affected.Conclusion MEK1 inhibits while MEK2 contributes to normal and human insulin-and insulin glargine-induced human bladder cancer T24 cell proliferation.