Objective：To assess the effect of GW5074 on the alveolar epithelial cell mesenchymal transition caused by high-dose small-volume radiation. Methods：In cell experiments，the morphological changes of cells before and after GW5074 treatment were observed. The expressions of C-Raf，p-C-Raf，Twist1，α-SMA and E-cadherin were detected by Western blot. After high-dose small-volume irradiation on mouse，the epithelial to mesenchymal transition of the injured tissues was observed by means of HE staining and immunofluorescence staining. Results：GW5074 alleviated effectively the morphological changes caused by high-dose irradiation. High-dose irradiation may activate C-Raf protein with the strongest effect at 48 hours after the irradiation. Pre-treatment by GW5074 and sh-Twist1 before irradiation can reduce the expressions of both Twist1 and α-SMA while increasing the expression of E-cadherin. The expression of p-C-Raf in the sh-Twist1 group was not significantly different from that in the irradiated group. Conclusion：By inhibiting the C-Raf/Twist1 signal path，GW5074 may effectively attenuate the alveolar epithelial cell mesenchymal transition caused by high-dose small-volume irradiation.