OBJECTIVE： To investigate the effects of NOS1AP rs12742393 polymorphism on therapeutic efficacy of repaglinide in the treatment of type 2 diabetes mellitus （T2DM） in Chinese Han patients. METHODS： A total of 100 newly-diagnosed T2DM Han patients without any hypoglycemic therapy were selected from the Affiliated Hospital of Xuzhou Medical University during Aug. 2015-Mar. 2017. Based on routine therapy， they were additionally given Repaglinide tablets 1.0 mg， tid， for consecutive 8 weeks at least. PCR-RFLP was used to detect the genotypes at NOS1AP rs12742393 in patients. The levels of FPG， PPG， HbA1c， FINS， PINS， HOMA-IR， TC， TG， HDL-C and LDL-C were observed before and after treatment. RESULTS： There were 1 case of withdrawal and 1 case of follow-up loss， and 98 patients accomplished the study. There were 39 cases of NOS1AP rs12742393 AA genotype， 42 cases of AC genotype and 17 cases of CC genotype， the frequency of them were 39.8％， 42.9％， 17.3％， which were in line with Hardy-Weinberg equilibrium （P＞0.05）. After 8 weeks， the levels of FPG， PPG， HbA1c， HOMA-IR， TC and TG were decreased significantly， compared with before treatment； the levels of FINS and PINS were increased significantly， compared with before treatment， with statistical significance （P＜0.05）. Before treatment， there was no statistical significance in each index among different genotypes （P＞0.05）. After treatment， the levels of FPG， PPG and HbA1c in all genotypes， the level of HOMA-IR in AA genotypes， the level of TC in CC genotype， the level of TG in AA and CC genotype were decreased significantly； the level of PINS in all genotype， the level of FINS in AC and CC genotype and the level of HOMA-IR in CC genotype were increased significantly； the levels of FPG and PPG in CC genotype were significantly higher than AA and AC genotype， and the decrease of two indexes than before treatment were significantly less than AA and AC genotype； the level of FPG in AC genotype was significantly higher than AA genotype； the level and increase than before treatment of FINS， and the level of HOMA-IR in AC and CC genotype was significantly higher than AA genotype； there was statistical significance in the change than before treatment of HOMA-IR among all genotypes （P＜0.05）. There was no statistical significance in other indexes among all groups before and after treatment（P＞0.05）. CONCLUSIONS： NOS1AP rs12742393 polymorphism may influence therapeutic efficacy of repaglinide in the treatment of T2DM in Chinese Han patients， and risk gene C may weaken therapeutic efficacy of repaglinide by influencing the levels of FPG， PPG， FINS and HOMA-IR.