We investigated the relationship between the improvement in insulin secretion and glycemic control in non-insulin-dependent diabetes mellitus (NIDDM). Fifty-two patients were classified into three groups according to their pretreatment fasting plasma glucose (FPG) level: Group A, FPG < 7.8 mM, n = 20; Group B, 7.8 mM < or = FPG < 11.1 mM, n = 17; and Group C, 11.1 mM < or = FPG, n = 15. A 75-g oral glucose tolerance test (OGTT) and a glucagon loading test were performed to evaluate insulin secretion before and after treatment. Plasma glucose levels during a 75-g OGTT were decreased significantly after treatment in all groups (P < 0.01). In Group A, there was no significant change in insulin secretion before and after treatment (1466 +/- 213 pM to 1565 +/- 191 pM, P = 0.35). In contrast, in Groups B and C, insulin secretion was poor and suppressed initially, but increased significantly when good glycemic control was obtained after treatment (respectively, 587 +/- 70 pM to 863 +/- 79 pM, P < 0.01, and 621 +/- 94 pM to 1236 +/- 232 pM, P < 0.01). The degree of improvement in insulin secretion in 75-g OGTT correlated positively with the degree of improvement in FPG level after treatment (r = 0.5, P < 0.001). However, the C-peptide response to glucagon did not change before and after treatment. In conclusion, impaired insulin secretion recovered by the good glycemic control in NIDDM with FPG levels above 7.8 mM. Therefore, strict glycemic control (FPG below 7.8 mM) seems important for maintaining good insulin secretion.