Random flap transplantation is widely used to repair and rebuild skin soft tissue. However, such flaps exhibit poor survival. Plastic surgeons seek to improve flap survival. We explored whether oxytocin improved skin flap survival. Overlength random skin flaps (9 × 3 cm) were established on backs of 80 healthy male SD rats randomly divided into two groups. One group was injected daily with oxytocin (1 mg/kg; test group) and the other with normal saline (control group). On postoperative day 2, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured. On postoperative day 7, the flap survival area was measured using transparent graph paper. Microvessel numbers were evaluated histologically by hematoxylin and eosin staining. VEGF expression was assessed immunohistochemically. Angiogenesis was evaluated via lead oxide-gelatin angiography and blood flow via laser Doppler flowmetry. In the test group compared with the control group, the flap survival rate and SOD activity were increased markedly, the MDA level was decreased, and according to hematoxylin and eosin staining, inflammation was significantly attenuated. In addition, the test group exhibited higher levels of VEGF and skin flap angiogenesis. Oxytocin improved flap survival rate by increasing microcirculation and angiogenesis and attenuating ischemia-reperfusion injury.