Ingestion of Ginkgo biloba Extract (EGb 761) may increase pancreatic β-cell function in both healthy subjects with normal glucose tolerance (NGT) as well as patients with Type 2 Diabetes mellitus (T2DM). Since hyperinsulinemia is a hallmark of T2DM, it is important to verify that increased insulin production is not due to increased insulin resistance.NGT subjects (n=10; age, 44.2±13.9 years old), impaired glucose tolerance (IGT) (n=8; age 51.3±6.6 years old) and T2DM subjects (n=8, 51.6±15.2 years old) completed a randomized, double-blind, placebo-controlled crossover study. After ingesting either EGb 761 (120mg/day as a single dose) or placebo during each 3-month arm, a 2-step euglycemic insulin clamp was performed.At the low insulin infusion rate (10mU/m 2 /min) the glucose metabolic rates (M values) were 3.5±1.5 vs. 3.0±0.5mg/kg (P=0.16), 3.0±0.4 vs. 2.8±0.8mg/kg (P=0.19) and 2.6±0.7 vs. 2.4±0.5mg/kg (P=0.09) for the placebo and EGb 761 cycles, in the NGT, IGT and T2DM subjects, respectively. At the high insulin infusion rate (40mU/m 2 /min) the M values were 7.3±2.3 vs. 8.1±2.5mg/kg (P=0.07), 6.2±1.6 vs. 6.5±2.1mg/kg (P=0.32) and 3.6±1.6 vs. 3.5±1.0mg/kg (P=0.34) for placebo vs. EGb 761 cycles, in the NGT, IGT and T2DM subjects, respectively.The ingestion of 120mg of EGb 761 as a single for 3 months did not produce insulin resistance in the non-diabetic or pre-diabetic subjects or exacerbate the disease in the T2DM subjects.