This study determines that VSMC signaling through ERK1/2-MAP-Kinase, v3-integrin and TGF1 dictates collagen type-I network induction in mesenteric resistance arteries (MRA) from type-1 diabetic (streptozotocin) or hypertensive (HT; angiotensin II, Ang II) mice. Isolated MRA were subjected to pressure-passive-diameter relationship. To delineate cell types and mechanisms, cultured VSMC were prepared from MRA and stimulated with Ang II (100nM) and high glucose (HG, 22mM). Pressure-passive-diameter relationship reduction was associated with increased collagen type-I deposition in MRA from HT and diabetic mice compared to control. Treatment of HT and diabetic mice with neutralizing TGF1-antibody reduced MRA stiffness and collagen type-I deposition. Cultured VSMC stimulated with HG or AII for 5-min increased ERK1/2-MAP-kinase phosphorylation, while a 48-h stimulation induced latent TGF1, v3-integrin, and collagen type-1 release into the conditioned media. TGF1 bioactivity and Smad2 phosphorylation were v3-integrin-dependent since 3-integrin-antibody and v3-integrin inhibitor (SB223245, 10µM) significantly prevented TGF1 bioactivity and Smad2 phosphorylation. Pretreatment of VSMC with ERK1/2-MAP-kinase inhibitor (U0126, 1µM) reduced v3-integrin, TGF1 and collagen type-1 content. Additionally, v3-integrin-antibody, SB223245, TGF1-siRNA and Smad2-siRNA (40nM) prevented collagen type-I network formation in response to AII and HG. Together, these data provide evidence that resistance artery fibrosis in type-1 diabetes and hypertension is a consequence of abnormal collagen type-I release by VSMC and involves ERK1/2, v3-integrin, and TGF1 signaling. This pathway could be a potential target for overcoming small arteries complications in diabetes and hypertension.