Abstract-A total of 75 in vivo endothelial function tests (intrabrachial artery infusions of endothelium-dependent[acetylcholine] and -independent [sodium nitroprusside] vasoactive agents) were performed in 18 type 2 diabetic patients (aged 58Ϯ2 years, body mass index 28.5Ϯ0.6 kg/m 2 , and fasting plasma glucose 229Ϯ11 mg/dL) and 27 matched normal subjects. These tests were performed before and 6 months after combination therapy with insulin and metformin and before and 6 months after metformin therapy only. Before insulin therapy, blood flow responses to acetylcholine (15 g/min) were significantly blunted in type 2 diabetic patients (7.5Ϯ0.7 mL ⅐ dL Ϫ1 ⅐ min
Ϫ1) compared with normal subjects (11.6Ϯ0.9 mL ⅐ dL Ϫ1 ⅐ min Ϫ1 , PϽ0.01). During insulin therapy, the acetylcholine response increased by 44% to 10.8Ϯ1.6 mL ⅐ dL Ϫ1 ⅐ min Ϫ1 (PϽ0.05). Insulin therapy also significantly increased the blood flow responses to both low and high doses of sodium nitroprusside. We conclude that insulin therapy improves endothelium-dependent and -independent vasodilatation. These data support the idea that insulin therapy has beneficial rather than harmful effects on vascular function.