Impaired blood flow to skin contributes to foot ulceration and amputation. The overall objective of this cross-sectional study was to examine the relationship between chronic physical activity and skin blood flow in Type 2 diabetes. To do so, diabetic and control subjects were separated into four groups based on a physical activity questionnaire: control exerciser (CE), control sedentary (CS), diabetic exerciser (DE), and diabetic sedentary (DS) subjects. After a physical exam and neuropathic testing, skin blood flow was measured noninvasively by continuous laser Doppler assessment of lower limb blood flow in response to various stimuli. Both groups of exercisers had enhanced baseline and ischemia reperfusion (IRP)-induced blood flow. Significant differences in maximal neurogenic dorsal foot skin perfusion were also present (P<.05): CE had greater perfusion than either diabetic group, but CS blood flow was higher than DS only. Since, nitric oxide (NO) is a potent vasodilator, concurrent real-time measurements of NO in cutaneous interstitial fluids were recorded. No significant differences in maximal levels of NO were found among the four groups during any flow condition. Fasting serum glucose levels and HbA(1c) were significantly inversely correlated with skin blood flow during heating. Chronic exercise is associated with enhanced skin blood under certain flow conditions in Type 2 diabetes compared with the sedentary state. As such, regular physical activity may be an invaluable tool in the prevention and reversal of defective skin vasodilation and resultant foot ulcers so common in diabetes.