Since Egr-1 plays a pivotal role in activation of many genes under stress conditions including hypoxia, we hypothesized that delivery of early growth response factor-1 (Egr-1) gene would modulate certain genes related to angiogenesis. To assess this hypothesis, we constructed an adenoviral vector harboring human Egr-1 cDNA and carried out transduction studies in HUVEC. cDNA microarray analysis of the RNAs from the transduced HUVEC revealed significant upregulation of angiogenesis-related genes such as Ang2, PDGF-A, PDGFR beta, anigomotin, and TGF-beta1. On the other hand, expression of Neuropilin 1, EDG1, Tie-1, Cox-1, and angiogenin were decreased compared to Ad-LacZ control. To evaluate angiogenic potential of Egr-1, Ad-Egr-1 was injected into tibialis anterior muscle of mouse (Balb/c) followed by explant culture in Matrigel under serum-free medium 3 days after transduction. Surprisingly, capillary-like structures were outgrowing from Ad-Egr-1-injected muscle on Day 3. The sprouting area was two-fold larger than the control Ad-LacZ injected group, suggesting that Egr-1 is pro-angiogenic. To confirm this result in vivo, we injected Ad-Egr-1 into four different sites of ischemic thigh muscle of mouse (C57BL/6) after femoral artery ligation. Compared to slow and incomplete revascularization of saline or Ad-LacZ-injected group, significant and fast increase in tissue perfusion was seen with Ad-Egr-1-injected group by day 8. Taken together, our results suggest that Egr-1 induces key angiogenesis-related genes and plays an important role in vascular recovery after occlusion.