Arterioles are embedded in the extensive connective tissue matrix of the interstitium. Mechanical interactions with the interstitium may affect the length-tension characteristics of arterioles, and thus affect their reactivity. However, no studies have adequately characterized the coupling between arterioles and the interstitium or investigated how the interstitium might change the physiological expression of arterioles. Therefore, the goal of this project was to investigate the mechanical interactions between arterioles and the interstitium and then to predict the physiological consequences of these interactions. We measured in situ the mechanical coupling of arterioles to the interstitium, the mechanical properties of the interstitium, and the structure of the interstitium in the hamster cheek pouch. We demonstrated that there are mechanical interactions between arterioles and the interstitium that are mediated both through direct connections and through the movement of extracellular fluid through the connective tissue network. We also found that the elastic modulus of the interstitium increases in the vicinity of the arteriole. Finally, both the mechanical coupling of arterioles to the interstitium and the mechanical properties of the interstitium are explained by the structure of the connective tissue matrix. The arterioles appear to be connected to adjacent fibroblasts and fibrocytes by collagen fibrils. These cells are in turn connected to the fiber matrix of the interstitium. Furthermore, the presence of these cells may explain the mechanical heterogeneity of the interstitium. We propose that the physiological role of the interstitium surrounding arterioles is to protect arterioles from stretching and deformation of the tissue while allowing these vessels to constrict freely.