Neurogenic inflammation, mediated by unmyelinated C-nerve fibers, is part of the acute neurovascular response to injury. Laser doppler flowmetry was used to measure the flare response to transcutaneous electrical nerve stimulation (TENS) and to compare this axon reflex vasodilatation with postischemic hyperemia in the skin of the foot in diabetic and nondiabetic subjects. Twenty-one control subjects and 57 diabetic patients (25 type I; 32 type II; 14 without complications; 14 with neuropathy and without retinopathy; 8 with retinopathy and without neuropathy; 21 with neuropathy and retinopathy) were enrolled in the study. Following TENS, an increase in skin blood flow was found at the dorsum of the foot without any significant difference between the different groups. Compared to the control group, axon reflex vasodilatation was significantly reduced in the group of patients with diabetic neuropathy and in the group of patients with diabetic neuropathy and retinopathy at the pulp of the hallux (61 +/- 15 versus -6 +/- 16; versus 23 +/- 5; p < 0.05, respectively). All investigated groups exhibited a significant increase in skin blood flow after arterial occlusion without any significant difference between the groups. A good association was observed between postocclusive and TENS-induced hyperemia at the dorsum of the foot (r = 0.39; p = 0.0002), but only a weak association was found at the pulp of the hallux (r = 0.24; p = 0.03). TENS-induced hyperemia was associated with a diminished sweat response (p = 0.03), but not with pathological cardiovascular function tests (p = 0.07). Electrical axon reflex vasodilatation is diminished in diabetic patients suffering from peripheral autonomic C-fiber injury, especially in skin rich in thermoregulatory blood flow. The diminished neurovascular response is independent of vascular alterations in diabetes mellitus.