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Simple Summary Postural changes induce arteriolar vasoconstriction in response to an increase in venous pressure in the limbs known as the venoarteriolar reflex (VAR). Previous studies reported that skin blood perfusion is impaired during the VAR in persons with type 2 diabetes mellitus (T2DM) with or without peripheral neuropathy, compared to control subjects. The aim of this study is to investigate the underlying mechanisms of the VAR in T2DM, with and without peripheral neuropathy. This study provides evidence that confirmed neuropathy alters the VAR by an alteration of the neurogenic response to leg dependency. Abstract The aim of this study is to investigate the underlying mechanisms of the venoarteriolar reflex (VAR) in type 2 diabetes mellitus (T2DM), with and without peripheral neuropathy. Laser Doppler flowmetry (LDF) recordings were performed on the medial malleus and dorsal foot skin, before and during leg dependency in healthy controls, in persons with obesity, in those with T2DM, in those with T2DM and subclinical neuropathy, and in those with T2DM and confirmed neuropathy. LDF recordings were analyzed with the wavelet transform to evaluate the mechanisms controlling the flowmotion (i.e., endothelial nitric oxide-independent and -dependent, neurogenic, myogenic, respiratory and cardiac mechanisms). Skin blood perfusion decreased throughout leg dependency at both sites. The decrease was blunted in persons with confirmed neuropathy compared to those with T2DM alone and the controls. During leg dependency, total spectral power increased in all groups compared to rest. The relative contribution of the endothelial bands increased and of the myogenic band decreased, without differences between groups. Neurogenic contribution decreased in controls, in persons with obesity and in those with T2DM, whereas it increased in subclinical- and confirmed neuropathy. In conclusion, this study provides evidence that confirmed diabetic neuropathy alters the VAR through the neurogenic response to leg dependency.