Vascular oscillation (vasomotion) occurs in the microcirculation and is thought to be a significant contributor to tissue perfusion. Our aims were to assess the relationship of vasomotion to perfusion in the cutaneous microcirculation of diabetic patients, to determine the influence on it of endothelium-dependent and nonendothelium-dependent vasodilatory stimuli, and to assess the relationship to perfusion and vasomotion of various biochemical markers of vascular function (HbA1c, LDL- and HDL-cholesterol, triglycerides, insulin resistance, high sensitive C-reactive protein, L- and E-selectin, soluble ICAM, von Willebrand factor) and microalbuminuria. Perfusion and vasomotion (spectral density at low and very low frequencies) were measured by laser-Doppler flowmetry after local heat and iontophoresis of ACh and sodium nitroprusside. Perfusion responses to all stimuli were impaired in patients with Type 2 diabetes (heat: F = 28.0, P < 0.001; ACh: F = 7.11, P = 0.003; sodium nitroprusside: F = 4.0, P = 0.028). Responses to endothelium-dependent stimuli were further impaired in microalbuminuric patients (heat: P = 0.035; ACh: P = 0.034). Vasomotion responses at low frequencies after endothelium-dependent stimuli were impaired in diabetic patients compared with that shown in controls (heat: F = 5.62, P = 0.002; ACh: F = 4.32, P = 0.015). Multivariate modeling showed microalbuminuria to be the only consistent predictor of perfusion and vasomotion responses. The results suggest that microalbuminuria in Type 2 diabetes reflects a generalized disturbance of microvascular function related to endothelium-dependent mechanisms.