The influence of dietary carbohydrate types on insulin action and muscle substrates was investigated. Seven healthy young men ingested two isoenergetic diets with 46-47% of energy as carbohydrates, 41% as fat, and 13-14% as protein, in which the carbohydrates either had a high glycemic index (HGI) or a low glycemic index (LGI) for 30 d, two times in a randomized crossover design. A euglycemic hyperinsulinemic clamp procedure was performed at the end of each dietary period. Whole-body glucose uptake was similar with both diets at a low plasma insulin concentration (370 pmol/L) but decreased (P < 0.05) at a high insulin concentration (2.4 nmol/L) with the LGI diet compared with the HGI diet. Higher plasma fatty acid concentrations during part of the day were found with the LGI diet compared with the HGI diet (P < 0.05). Initially, blood glucose and plasma insulin concentrations were lower (P < 0.05) during part of the day with the LGI than with the HGI diet, but after 30 d of the diet this difference diminished. Muscle glycogen and triacylglycerol concentrations were increased (P < 0.05) by 14% and 22%, respectively, with the HGI diet compared with the LGI diet, and muscle triacylglycerol concentrations did not correlate with insulin action. It is concluded that when ingesting a diet with an energy composition common in Western countries, switching the carbohydrates from high to low GI sources decreases insulin action on whole-body glucose disposal at a high but not at a physiologic plasma insulin concentration. Furthermore, adaptation in terms of carbohydrate digestion and/or absorption to a diet rich in LGI carbohydrates may take place over 4 wk.