Using human tissues with clinical relevance and challenging to obtain, as well as the first miRNA gene mutant rat model that we are aware of, we have (i) established miRNA expression patterns in human resistance arterioles associated with endothelial dysfunction in T2DM, (ii) discovered an important role of miR‐29 in promoting NO production and endothelial function, and (iii) identified miR‐29 as a potent agent for restoring endothelium‐dependent vasodilation in human T2DM arterioles through a mechanism that in significant part involves modulation of Lypla1 expression. Here, LYPLA1 is linked to type 2 diabetes mellitus.