Objective: To assess the effect of vitamin D administration on the skin blood flow response to occlusion and heat. Design: Cross-sectional study. Methods: Twenty age matched subjects; 10 who had diabetes and 10 who were controls were administered 4,000 IU of vitamin D3 for 3 weeks at breakfast. The function of the endothelial cells was evaluated in 2 ways; first, the response to 4 minutes of vascular occlusion of the skin was measured with a laser Doppler flow meter. Second, the skin blood flow response to local heat at 42 degrees C for 6 minutes was examined. Results: The results of the experiments showed that the blood flow response to heat was reduced after 3 weeks administration of vitamin D in the subjects with diabetes and in the control subjects (p<0.05). The response to occlusion was not significantly different within each group before and after vitamin D administration, but the group with diabetes had a significantly lower blood flow response to occlusion than did the controls (p<0.05). Conclusions: Acute doses of vitamin D may impair nitric oxide production and reduce blood flow to tissue during stressors in people with diabetes.