Medial thickening and vascular hypertrophy of resistance arteries can lead to cardiovascular complications associated with diabetes. While previous studies have established a role of Type 1 diabetes on vascular remodeling, we recently extended these observations to Type 2 diabetes and reported increased collagen deposition due to alterations in matrix metalloproteinase expression and activity in mesenteric resistance arteries. These studies also showed that remodeling response was mediated by endothelin-1 (ET-1) via activation of ET_A receptors whereas blockade of ET_B receptors exacerbated the remodeling. However, the effectiveness of glycemic control strategies in preventing these vascular changes including activation of the ET system still remained unclear. Also, very little is known of whether and to what extent does reorganization of the extracellular matrix (ECM) affect vascular compliance and vasomotor tone. Accordingly, this study assessed structural remodeling of mesenteric microvessels, vascular compliance and myogenic tone and the role of matrix metalloproteinases (MMP) in mediating these processes. Spontaneously diabetic, non-obese Goto-Kakizaki (GK) rats, a model for Type 2 diabetes and normoglycemic Wistar rats were used for the studies. A subset of GK rats were administered metformin to achieve euglycemia. Glycemic control normalized the increased media-to-lumen ratios (M/L) and myogenic tone seen in diabetes as well as normalizing plasma ET-1 levels and mesenteric ET_A receptor expression. There was increased collagen synthesis in diabetes paralleled by decreased collagenase MMP-13 activity, while glycemic control attenuated the process. These findings and our previous study taken together suggest that hyperglycemia-mediated activation of ET-1 and ET_A receptors alter vascular structure and mechanics in Type 2 diabetes.