Objective To investigate the function of pancreatic islet β-cells in first degree relatives with normal glucose tolerance in type 2 diabetes mellitus (T2DM) families. Methods The first degree relatives of T2DM families with normal glucose tolerance (T2DM first degree relatives group, n=94) and normal glucose tolerance subjects without diabetes mellitus family history (normal control group, n=98) were enrolled. Oral glucose tolerance test and serum insulin release test were taken for obtaining the whole body insulin sensitivity index [ISI(Matsuda)], early insulinogenic index and total insulinogenic index (IGI30 and IGI), respectively. Glucose disposition indexes (DI) including DI30 [ISI(Matsuda)×IGI30] and DI [ISI(Matsuda)×IGI] were calculated to evaluate the early and total insulin secretion of islet β-cells. Results ISI(Matsuda) in T2DM first degree relatives group and normal control group were 107.39±41.88 and 105.18±44.18, respectively, DI were 631.04±179.25 and 665.66±230.71, respectively, and there was no significant difference in ISI(Matsuda) and DI between these two groups (P>0.05). However, DI30 in first degree relatives group (1 248.44±894.41) was significantly lower than that in normal control group (1 558.35±1 015.66)（P<0.05）. Conclusion There is early insulin secretion deficiency of pancreatic islet β-cells in first degree relatives with normal glucose tolerance in T2DM families, while the insulin sensitivity still remains normal.