Elevated dietary salt intake has previously been demonstrated to have dramatic effects on microvascular structure and function. The purpose of this study was to determine whether a high salt diet modulates physiological angiogenesis in skeletal muscle. Male Sprague-Dawley rats were placed on a control diet (0.4% NaCl by weight) or high salt diet (4.0% NaCl) prior to implantation of a chronic electrical stimulator. Following seven consecutive days of unilateral hindlimb muscle stimulation, animals on control diet demonstrated a significant increase in microvessel density in the tibialis anterior muscle of the stimulated hindlimb relative to the contralateral control leg. High salt-fed rats demonstrated a complete inhibition of this angiogenic response, as well as a significant reduction in plasma angiotensin II (ANGII) levels compared with control animals. To investigate the role of ANGII suppression in the inhibitory effect of high salt diet, a group of rats fed high salt were chronically infused with ANGII at a low dose. Maintenance of ANGII levels restored stimulated angiogenesis to control levels in animals fed a high salt diet. Western blot analysis indicated that inhibition of angiogenesis in high salt-fed rats was not due to changes in VEGF or VEGF receptor type 1 protein expression in response to stimulation; however, the degree to which VEGF receptor 2 protein increased with stimulation was significantly lower in high-salt fed animals. This study demonstrates an inhibitory effect of high salt intake on stimulated angiogenesis, and suggests a critical role for ANGII suppression in mediating this antiangiogenic effect.