Objective To investigate the effects of ecdysterone on the survival of the dorsal random-pattern skin flap with large length-to-width ratio in rats and its possible mechanisms. Methods Twenty-four healthy adult SD rats (male and/or female) weighing 200-250 g were randomly divided into the experimental group and the control group (n=12 per group).A caudally based dorsal random pattern skin flap, measuring 8 cm × 2 cm, was symmetrically raised. Ecdysterone (5 mg/kg) and normal sal ine (5 mg/kg) were injected into the abdominal cavity of rats in the experimental group and the control group at 10 minutes before operation and from the first to the fifth day after operation, respectively. The general condition of the rats was observed after operation. At 7 days after operation, the survival rate of the flap was detected, the superoxide dismutase (SOD) activity and the malonyldialdehyde (MDA) level were tested, HE and immunohistochemistry staining observation of the flap were performed. VIII factor dried microvessels in the middle part of the flap (4 cm far away from pedicle) were counted. Results All the rats survived until the end of the experiment. At 7 days after operation, the survival rate of the flap was 62.323% ± 7.046% in the experimental group and 47.753% ± 2.952% in the control group (P lt; 0.001); SOD activity was (54.560 ± 4.535) U/mgprot in the experimental group and (23.962 ± 3.985) U/mgprot in the control group (P lt; 0.001); MDA level was (8.445 ± 0.992) nmol/mgprot in the experimental group and (14.983 ± 0.929) nmol/mgprot in the control group (P lt; 0.001). Histology observation: compared with the control group, the inflammatory cells infiltration was less and the hyperplasia of fibers was more obvious in the experimental group. The microvessel counting in the middle part of the flap was 17.817 ± 2.420 in the experimental group and 8.967 ± 2.000 in the control group (P lt; 0.001). Conclusion Perioperative intraperitoneal injection of ecdysterone can promote the survival of the random-pattern skin flaps with large length-to-width ratio. Its mechanism may be related to its effects of improving SOD activity, decreasing l ipid peroxidation, and promoting angiogenesis of skin flaps.