Objective To investigate whether the interaction of hypertension and diabetes aggravates endothelial dysfunction and leads to smooth muscle dysfunction. Methods Noninvasive methods were used to the investigated patients with type 2 diabetes mellitus (2-DM) (Group 1), patients with hypertension (Group 2) and patients with both 2-DM and hypertension (Group 3), as well as a normal control group (Group 4) by studying a brachial artery without evidence of atherosclerotic plaque formation. Results Results showed that endothelium-dependent vasodilation decreased significantly in Group 1 (5.74%±3.32%, P<0.05), Group 2 (4.14%±2.93%, P<0.01), and Group 3 (2.78%±2.08%, P<0.001) as compared to the control (9.45%±3.88%). The nitroglycerin-induced vasodilation (smooth muscle function) in Group 3 was significantly decreased as compared to the control group (14.11%±4.63% vs 23.53%±6.77%, P<0.001), but there were no differences in nitroglycerin-induced vasodilation between Group 1, Group 2 and Group 4. On univariate analysis, a reduced vasodilator response to nitroglycerin was associated with endothelium-dependent vasodilation (r=0.54, P<0.001). Conclusion Our results indicate that the interaction of 2-DM and hypertension aggravates endothelial dysfunction and further impairs the smooth muscle function.