Objective To investigate the effects of glutathione (GSH) on survival of the random skin flap in rats and the probable mechanism that contribute to this effect. Methods Twenty SD rats with 200-250 g in weight, were randomly divided into the experimental group and control group(n=10). Random flap of 8 cm×2 cm in size was made on the back of each rat with the pedicel on the angular of the scapular. GSH(250 mg/kg) and NS of the same dose were injected into the abdominal cavity of rats in the experimental groupand the control group immediately after the operative, 1st and 2nd days respectively. The rats were killed on the 7th day after the operation. The tissue pathology, the survival rate of the flap, the superoxide dismutase(SOD) activity and malonyldialdehyde (MDA) level were compared between two groups. Results The mean survival rate of the flap on the 7th day in the experimental group（56.77%±10.67%） was higher than that in the control group(40.16%±7.12%)(Plt;0.05).SOD activity in experimental group （306.06±84.87 U/mgprot）was higher than that in the control group （224.79±27.12 U/mgprot）, while MDA level （3.835±0.457 nmol/mgprot）was lower than that in the control group (6.127±0.837 nmol/mgprot)(Plt;0.05). Histological observation showed that the neutrophil infiltration was less in experimental group than that in the control group; that the experimental group was surperior to the control group in angiogenesis, fibroblasts, fair cells and cuaneous gland. Conclusion The intraperitoneal use of GSH may promote the survival rate of the random flaps and the possible mechanism for improvement may lies in that the GSH can reduce the level of oxygen free radical and lipidperoxidation,and lessen neutrophil infiltration.