Conventional (high dose) radiation has been implicated in Hypoxia Inducible Factor-1 (HIF-1) regulation in tumor cell lines. However, little is known of the effects of radiation on the vascular endothelium, specifically in the regulation of pro-vasculogenic signaling. Here we show that low dose radiation promotes vasculogenesis by augmenting HIF-1 up-regulation of stromal-cell derived factor-1 (SDF-1) in endothelial cells outside the tumor milieu, stimulating endothelial progenitor cell (EPC) migration. Using in-vitro culture of humans endothelial cells, we show that HIF-1 is translationally up-regulated with radiation, resulting in increased nuclear localization by 48 hrs post radiation independent of hypoxia. Hypoxia acts as an additive stimulus for HIF-1 up-regulation, augmenting nuclear localization. HIF-1 has been shown to stimulate vasculogenesis though SDF-1 up-regulation, inducing localization of EPCs to areas of hypoxia. We show that low-dose radiation increases HIF-1 binding to hypoxia response elements (HRE) sites in endothelial cells, resulting in elevated expression profiles for SDF-1 and VEGF, both potent stimulators of vasculogenesis. Although previous studies have examined the effect of LDRT on progenitor cell recruitment we demonstrate for the first time a LDRT induced, HIF-1 independent, stimulation of SDF1 and subsequent EPC activation. Our research offers new insight into the pro-angiogenic and pro-vasculogenic effects of ionizing radiation. Because of the central nature of H1F1 and SDF1 to these signaling pathways, it is clear that ionizing radiation may have a profound effect on these processes.