Starches that are high in amylopectin are digested and absorbed more quickly than starches with a high amylose content and produce insulin resistance in rats during long-term feeding. The aim of this study was to determine whether amylopectin-induced insulin resistance could be prevented or reversed by a period of high amylose feeding. We employed a randomized design in which two groups of rats were fed either the high amylose and then the high amylopectin diet for two consecutive 8-wk periods or vice versa (high amylopectin and then high amylose). Four other groups were fed either a high amylose or a high amylopectin diet for 8 or 16 wk. All rats were fed two 10-g meals per day (300 kJ/d), and insulin sensitivity was assessed by intravenous glucose tolerance test (IVGTT) after 8 or 16 wk of feeding. We found no difference in glucose tolerance between any group at any time point. Insulin responses, however, were 50% higher (P < 0.01) after 16 wk of high amylopectin feeding [area under the plasma insulin curve (AUC) = 18.1 +/- 1.4 nmol.L-1 x 15 min] compared with high amylose feeding (AUC = 13.0 +/- 1.2 nmol.L-1 x 15 min). The two groups which received both diets developed a similar degree of insulin resistance, equivalent to that after 16 wk of high amylopectin feeding. The findings suggest that amylopectin-induced insulin resistance cannot be reversed or prevented by either a subsequent or previous period of amylose feeding. Taken together, the data suggest that the nature of starch in the Western diet influences the development of noninsulin-dependent diabetes mellitus in humans.