Objective To observe the changes of granulocyte-macrophage colony stimulating factor(GM-CSF) expression in mice with radiation and incision combined injury during wound healing and analyze its therapeutic effect, paving a way for exploring the effect of GM-CSF on healing of radiation combination injury. Methods A total of 56 Kunming mice (20-22 g) were randomly divided into two groups: the experimental group and control group (n=28 for each group). Mice in the experimental group were made into irradiated injury plus skin wound by incising the back immediately after exposing to 6 Gy ⁶⁰Co γ radiation. Pure incision injury without radiation exposure was made in the mice in control group. Mice were sacrificed on day 1, 3, 5, and 7 (7 mice for each time) after model establishment, and skin and thin layer of muscle tissues around the wound were collected. Real-time PCR and immunohistochemical analysis were used to examine the mRNA and protein expression of GM-CSF. Moreover, radiation and incision combined injury models were also established in 40 species-, body mass-matched mice using same method described above and the model mice were divided into two groups: treatment group and blank control group (n=20 for each group). The wounds were treated with rhGM-CSF gel (6 000 ng/mL) in the treatment group at 0, 1, 3, 4, 5, 7, 9, 11, and 14 d after model establishment, while blank gel was given to the blank control group. Then the therapeutic effects of rhGM-CSF gel on wound healing were evaluated based on the wound residual area and the level of collagenous fiber around the wound. Results The expression levels of GM-CSF protein and mRNA were significantly lower in the radiation and incision combined injury models during 1-3 days compared with the control group (P<0.05). The expression of GM-CSF was gradually decreased during 5-7 days in the control group, while it kept unchanged in the experimental group. During the 14 days treatment with rhGM-CSF gel, the wound areas were significantly smaller than those of the blank control group (P<0.05). Meanwhile, Masson staining showed notable proliferation, widely distributed, and tightly arranged collagenous fiber after rhGM-CSF gel treatment at the injury sites. Conclusion The level of GM-CSF is lower in radiation and incision combined injury compared with the control, and continuous rhGM-CSF (6 000 ng/mL) treatment can greatly promote the healing of radiation and incision combined injury.