Post-prandial hyperglycemia (PPHG) is an independent risk factor for the development of macrovascular complications. It is now recognized that normalizing post-prandial blood glucose is more difficult than normalizing fasting glucose. Many factors affect the post-prandial blood glucose excursion. The glycemic index of the meal depends on the nature of the ingested food and starch composition. Gastric emptying is influenced by various factors including gut hormones such as GIP and GLP1, which potentiate insulin secretion, especially in its acute first phase, now referred to as an incretin effect. They also modulate glucagon secretion. Post-prandial hyperglycemia is limited by uptake of glucose by the liver and by inhibition of endogenous glucose production in this organ. In healthy controls, hepatic glucose production is halved after a meal, whereas in glucose-intolerant individuals and type 2 diabetics this inhibition is impaired (20-30% versus 50%). The persistence of endogenous glucose production during the post-prandial phase appears to be the main culprit in the PPHG. This reduced decrease in endogenous glucose in glucose intolerant and type 2 diabetic patients depends not only on the first acute phase of insulin secretion, but above all on the non-suppressed glucagon level during the post-prandial phase. Glucagon levels fall in healthy control subjects during the post-prandial phase. Although peripheral glucose uptake by insulin-dependent tissues is altered in type 2 diabetic patients, it does not appear to be the major cause of the PPHG as there are patients with insulin resistance but without post-prandial hyperglycemia.