Critical limb ischemia (CLI), results from a severe blockade of the arterial vessels, is usually correlated to atherosclerosis. Circulating angiogenic cells (CACs) constitute a good alternative as CLI cell therapy due to their vascular regenerative potential, although the mechanisms of action of these cells as well as their response to pathological conditions remains unclear. Previously, we have shown that the incubation ex vivo of CACs with factors secreted by atheroma plaques promotes the activation and mobilization of these cells. Herein, we have evaluated the long-term effect of CACs administration in CLI mice, whether pre-stimulated or not with atherosclerotic factors.