Angiogenesis, under normal conditions, is a tightly regulated balance between pro- and anti-angiogenic factors. The goal of this study was to investigate the mechanisms involved in the control of the skeletal muscle angiogenic response induced by electrical stimulation during the suppression of plasma renin activity (PRA) with high salt diet. Rats fed 0.4% or 4% salt diets were exposed to electrical stimulation for 7 days. The tibialis anterior (TA) muscles from stimulated and unstimulated hindlimbs were removed and prepared for gene expression analysis, CD31/TUNEL double staining assay, and Bcl-2 and Bax protein expression by Western blot. Rats fed a low salt diet showed a dramatic angiogenesis response in the stimulated limb as compared to the unstimulated. This angiogenesis response was significantly attenuated when rats were placed on a high salt diet. Microarray analysis showed that in the stimulated limb of rats fed a low salt diet, many genes related to angiogenesis were upregulated. In contrast, in rats fed a high salt diet, most of the genes upregulated in the stimulated limb function in apoptosis and cell cycle arrest. Endothelial cell apoptosis, as analyzed by CD31/TUNEL staining, increased by 4 fold in the stimulated limb compared to unstimulated. There was also a 48% decrease in the Bcl-2 to Bax ratio in stimulated compared to unstimulated legs of rats fed a high salt diet, confirming severe apoptosis. This study suggests that the increase in endothelial cell apoptosis in TA muscle might contribute to the attenuation of angiogenesis response observed in rats fed a high salt diet.