Abstract: Objective：To explore the value of arginine stimulation test in evaluating the first-phase insulin secretion and its guiding role for the treatment of type 2 diabetes mellitus. Methods：Totally 80 cases with newly diagnosed type 2 diabetes mellitus (NT2DM）, 162 type 2 diabetes subjects with effective treatment by lifestyle intervention or oral hypoglycemic drugs therapy(LIODT）, 160 subjects with insulin therapy (IT), and 40 subjects with normal glucose level (NC) were admitted in the study in Department of Endocrinology, and the Physical Examination Center of Zhongshan Hospital, Fudan University. Arginine stimulation test was performed to assess the first-phase insulin secretion. Fasting and 2, 4, 6 min glucose (G), insulin (I) and c-peptide (CP) after arginine stimulating were tested. Results：The Δ I, Δ I/G, Δ CP/G in arginine stimulation test were decreased significantly in the patients with NT2DM, LIODT and IT groups than those in the NC group (P＜0.01). Among different groups of type 2 diabetes, Δ I, Δ CP, Δ I/G, ΔCP/G were decreased significantly in the IT group than the other two groups (P＜0.01). The normal cut-off point of AIR was Δ I≥23.09 mU/L. Δ I, Δ I/G, Δ CP/G negatively correlated with fasting plasma glucose (FPG) and HbA1c, and Δ I, Δ CP, Δ I/G, Δ CP/G were negatively correlated with daily dose and numbers of oral diabetic medications after adjustment for gender, age, BMI. In the known type 2 diabetes groups (including LIODT and IT group), the optimal cut-off values from ROC curve for initiating insulin therapy were ΔI≤12.23 mU/L，and ΔCP≤0.97 ng/mL（P＜0.01）. Conclusions：Arginine stimulation test can effectively assess the first-phase insulin secretion. In type 2 diabetes, ΔI≤12.23 mU/L or ΔCP≤0.97 ng/mL suggest severely lost of first-phase insulin secretion, and need insulin therapy.