【Objective】To explore the effect of alpha2-macroglobulin（α2M）on superoxide anion（.O 2 - ）content， superoxide dismutase（SOD）activity and the process of cell-to-myofibroblast transformation in human skin fibroblasts （HSF）after X-ray irradiation.【Methods】HSF cells were irradiated with 0，5，10，15 and 20 Gy X-ray. The change of . O 2 - content and SOD activity in the supernatant of cell culture medium were measured on the first day after irradiation. The protein expression of alpha-smooth muscle actin（α-SMA）was detected by Western blot on the fifth day after irradia? tion. The most sensitive radiation dose is selected. HSF cells were irradiated with the above sensitive dose. Respectively， 1h before irradiation，1 h after irradiation，the experimental group cell culture medium was added to a final concentration of 0.25 mg/mL，0.5 mg/mL of α2M. The change of .O 2 - content，SOD activity and the protein expression of α-SMA weredetected.【Results】HSF cells were irradiated with 5~20 Gy doses of X-ray. .O 2 - content increased，SOD activity de? creased and α-SMA protein expression increased gradually（P<0.05）. The addition of α2M at 1 h after 10Gy X-ray irradi? ation reduced the .O 2 - content，increased the SOD activity and downregulated the protein expression of α-SMA in HSF cells（P<0.05）. There was no significant change in the administration at 1 h before irradiation. 【Conclusion】HSF cells increased .O 2 - content significantly，while SOD activity decreased，and the tendency to transform myofibroblasts after X- ray irradiation. α2M can reduce the .O 2 - content，increase the SOD activity in HSF cells and inhibit the transformation of fibroblasts into myofibroblasts after irradiation. Indicating that α2M can play a role in radiation protection by anti-oxida? tion and anti-fibrosis.