We studied the metabolic effects of 2-wk fructose feeding as the sweetener in the diet of seven noninsulin- dependent diabetic individuals. The data demonstrated reduced postprandial hyperglycemia to an oral glucose challenge after 14 days without a significant difference in insulin response. There was no change in the markedly blunted glucose response to a fructose challenge but a significantly lower insulin response (area under the 3-h curve) was observed after 14 days of fructose feeding. There was reduced postprandial hyperglycemia after 14 days of fructose feeding with test meals as compared with baseline, without significant differences in insulin response. We also found no significant difference in free fatty acids, cholesterol, high-density lipoprotein (HDL) cholesterol, pyruvate, lactate, or uric acid after fructose feedings. There was a 13% increase in triglyceride levels after 14 days in 5 subjects with initial fasting hypertriglyceridemia (>150 mg/dl). Insulin receptor binding to isolated adipocytes did not change after 14 days of fructose feeding.