This experimental study investigates the feasibility of pretreating the abdominal skin of a rat with subdermal injections of adenovirus encoding angiopoietin-1 in order to improve postoperative survival of the skin flap. An epigastric skin flap was used as the model in this study. Rats received subdermal injections of adenovirus encoding either angiopoietin-1 (treatment group) or green fluorescent protein (treatment control), or they received no treatment (control group). Subdermal injections were made 2 days prior to surgery, and skin flap survival was assessed 7 days afterwards as a percentage of necrotic area over total skin flap area. The treatment group which received adenovirus-mediated angiopoietin-1 had a median percent necrotic area of 11.01%, a significant decrease from the control group, which had a median percent necrotic area of 32.24% (P < 0.001). The results of this study suggest the possibility of using adenovirus-mediated angiopoietin-1 gene therapy to promote therapeutic angiogenesis in patients who undergo reconstructive procedures.