Abstract: Objective To evaluate the effect of chronic hyper glycaemia on the pancreatic β-cell response in diabetic patients. Me thods We investigated the effect of various blood glucose levels on the β-cell response to stimulation with a standard oral glucose or intravenous gl ucagon in 118 patients with type 2 diabetes. Results The rele ases of C-peptide and insulin were decreased with increased level of fasting blood glucose (P<0.01)after oral glucose stimulation, and were increased with decreased levels of fasting blood glucose after glucagon stimulation wh ile C-peptide and insulin release keeping higher when fasting blood glucose lev el was above 9 mmol/L. The release of insulin showed an inverse association to HOMA-IR (P<0.01)after oral glucose stimulation and it showed a positive association with HOMA-β(P<0.01)after glucagon stimulation. C onclusions The evaluation of function of β-cell secretion is confused by glucose toxicity because severe hyperglycaemia significantly reduces C-pep tide and insulin release after oral glucose stimulation, but this is not the cas e after glucagon stimulation in type 2 diabetic patients.