This study was designed to determine the effect of a novel insulin secretagogue, nateglinide, on the glycemic response curve and early insulin secretion following oral glucose load in impaired glucose tolerance (IGT) subjects. Thirteen subjects were given a 75 g oral glucose tolerance test (75 g OGTT), the findings of which resulted in the diagnosis of IGT. The subjects returned to our hospital immediately. Eight subjects, in whom neither body weight nor life style (daily diet and exercise) was significantly altered during this period, were given 90 mg of nateglinide 5 min before a second oral glucose load in order to examine restoration of impaired early insulin secretion. Nateglinide administration resulted in the almost normalization of the glycemic response curve with restoration of impairment in early insulin response at 30 and 60 min after an oral glucose load. The area under the secreted insulin-time curve was not changed significantly by nateglinide administration. A single dose of nateglinide was shown to almost normalize the glycemic response curve after a 75 g OGTT and to restore impairment in early insulin response in IGT subjects.