Arterial stiffness is a key marker in metabolic diseases and can be evaluated by arterial compliance. Most compliance measurements are performed in large conduit arteries in advanced stage of metabolic diseases, which may not provide information on mechanisms associated with the initiation of the pathology. For this reason, we compared arterial compliance of two different size arteries: carotid and a smaller artery (thoracodorsal artery, TDA). The arterial compliance was compared between control and high fat-fed mice for 6 weeks. We show that the compliance of the TDAs was dramatically reduced in high fat-fed mice whereas the compliance of the carotids remained unchanged. An abundance of collagen deposition in the media/adventitia of the carotids and TDAs was observed in high fat-fed mice. These results demonstrate that the structural and mechanical properties of small arteries are rapidly altered even after only 6 weeks of high fat feeding.