The aims of this study was to investigate whether ecdysterone is able to exert glucose-lowering effect on hepatocytes or stimulate the secretion of insulin. HepG2 cell line was used for glucose consumption (GC) studies. At moderate high glucose concentration (11.1 mmol/L), GC of HepG2 cells was increased by 44% to 77% with ecdysterone 1 x 10(-6) to 1 x 10(-4) mol/L, which was comparable to that with 1 x 10(-3) mol/L metformin. The glucose-lowering effect of ecdysterone decreased as the glucose concentration of medium increased. The maximal potency was reached in the presence of 5.5 mmol/L glucose, and the effect was disappeared as the glucose consumption was increased to 22.2 mmol/L. This effect was independent on insulin concentration, which was similar to that of metformin and was different from that of troglitazone, whose glucose-lowering effect was insulin-dependent. Troglitazone had a better antihyperglycemic potency than metformin when insulin was added. Simultaneously, a significant toxicity of troglitazone to HepG2 cells was observed. betaTC3 cells were not stimulated by ecdysterone, that is, no secretogogue effect of ecdysterone was observed. The results indicate that ecdysterone is able to exert the glucose-lowering effect in hepatocytes which is insulin-independent, but has no effect on insulin release.