Exercise training induces adaptations of skeletal muscle vasculature that appear to be beneficial in prevention and treatment of type 2 diabetes (T2D). The distribution of vascular adaptation to different types of exercise training are heterogeneous in part because skeletal muscle arteriolar trees are heterogeneous and because muscle fiber type composition and fiber recruitment patterns that produce different modes of exercise are heterogeneous. Thus, training-induced adaptations of vascular structure and vascular control in skeletal muscle are not homogeneously distributed throughout skeletal muscle or along the arteriolar tree within a muscle. Results will be summarized which indicate that exercise training induced changes in vascular gene expression differ along the arteriolar tree and by skeletal muscle fiber type composition. Using the OLETF rat model of T2D we observed that endothelium-dependent dilation (EDD) is blunted by T2D differentially in muscle with different muscle fiber type composition and exercise training restores EDD in a fiber type dependent manner 1-3 as exercise training improves EDD non-uniformly in the arterial tree of skeletal muscle 1-3. Both interval sprint (SPRINT) and endurance training (EX) increased ACH-induced EDD in the gastrocnemius FA and the RG2a but only EX improved vasodilation of the WG2a. Neither training program altered responses of the soleus FA. Insulin produced vasodilation of the RG2a in EX animals only. When ET-1 receptors were blocked with tezosentan RG2a’s from all three groups exhibited vasodilation to insulin. Similar results were seen in the WG2a. These results led us to conclude the EDD is blunted in T2D skeletal muscle arterioles in a muscle fiber type dependent manner. EX and SPRINT increased EDD in some arterioles but not all. Results also indicate that insulin signaling in arteriolar endothelium differs among types of skeletal muscle and among different branch orders in skeletal muscle of arteriolar trees 1, 3. EX also improved insulin-induced EDD non-uniformly in the arterial tree of skeletal muscle. Thus, results indicate that the blunting of EDD induced by T2D differs with muscle fiber type composition of skeletal muscle and that different exercise training programs reverse this dysfunction differently in arterioles from skeletal muscles of differing fiber type composition 2, 3. Indeed, it is striking that exercise training improves EDD non-uniformly even within the arteriolar tree of a given muscle, the gastrocnemius 3. We determined transcriptional profiles for samples of arterioles/arteries from the same rats using techniques described previously 4-7. Results show that EX caused the largest number of changes in gene expression in the soleus and white gastrocnemius 2a arterioles with little to no changes in the feed arteries. In contrast, SPRINT caused substantial changes in gene expression in the feed arteries. IPA canonical pathway analysis revealed 18 pathways with significant changes in gene expression when analyzed across vessels and revealed that EX induces increased expression of some genes in all arterioles examined (Shc1, desert hedgehog protein (Dhh), adenylate cyclase 4 (Adcy4), G protein binding protein, alpha (Gnat1), and Bcl2l1) but decreased expression of ubiquitin D (Ubd) and cAMP response element modulator (Crem) across all arterioles. EX increased expression of endothelin converting enzyme (Ece1), Hsp90b, Fkbp5, and Cdcl4b in 4 of 5 arterioles. SPRINT had effects on expression of Crem, Dhh, Bcl2l1 and Ubd that were similar to EX. SPRINT also increased expression of Nfkbia, Hspa5, Tubb 2a and Tubb 2b, and Fkbp5 in all 5 arterioles and increased expression of Gnat1 in all but the soleus second order arterioles. Many contractile and/or structural protein genes were increased by SPRINT in the gastrocnemius feed artery but the same genes exhibited decreased expression in red gastrocnemius arterioles. Results suggest that it is unlikely that hemodynamic forces are the only exercise-induced signals mediating the regulation of vascular gene expression. We conclude that training-induced changes in arteriolar gene expression patterns differ by muscle fiber type composition and along the arteriolar tree. If these adaptions occur in a sufficient amount of muscle mass, exposure to hyperglycemia and hyperinsulinemia will decrease along with the risk of microvascular complications throughout the body. It is postulated that exercise sessions in programs of sufficient duration, that engage as much skeletal muscle mass as possible and recruit as many muscle fibers within each muscle as possible, will produce the greatest benefit. The added benefit of combined resistance and aerobic training programs and of high intensity exercise programs is not simply “more exercise is better”.