Since insulin resistance was first associated with type 2 diabetes and later with cardiovascular disease and hypertension, there has been considerable interest in the role of dietary and environmental factors. Sucrose and fructose have been a particular research focus. Research on animals, particularly rodents, has shown a clear and consistent effect of high-sucrose and high-fructose diets in decreasing insulin sensitivity. Experiments in humans have produced very conflicting results, with limited evidence for a negative effect on insulin sensitivity at higher intakes of fructose or sucrose (generally > 30% of daily energy from sucrose and > 15% of daily energy from fructose). Observation studies in humans have not shown a link between sucrose consumption and insulin sensitivity independent of other dietary factors. This is in contrast with several small studies that showed an improvement in insulin sensitivity after subjects followed dietary advice to lower the glycemic index of their food choices (where sugars were not a target for change). However, the pattern of postprandial glucose and insulin responses elicited by sucrose and fructose differs substantially from that elicited by starches, with lower troughs elicited by sucrose and fructose 2-3 h after eating. These differences in the pattern of postprandial responses offer a potential explanation for the conflicting results on insulin sensitivity, with the possibility that increases in insulin exposure may affect insulin sensitivity through down-regulation of insulin action.