Radiation-induced lung injury (RILI) is one of the most common and severe side effects of thoracic radiotherapy. Therefore, novel therapeutic approaches to improve the effectiveness of RILI treatment are required. The present study was designed to determine the effectiveness of a traditional Chinese medicine regimen, Shenqi Fuzheng injection (SFI), in the treatment of RILI. SFI is composed of extracts from codonopsis pilosula and radix astragali. Here, we determined the protective effects of SFI on RILI with a single-dose irradiation (RT) of 12 Gy in C57BL/6 8-week-old mice. The mice were divided into four groups treated with i) phosphate-buffered saline (PBS; pH 7.4, 20 ml/kg/day) alone as normal a control; ii) SFI only (20 ml/kg/day); iii) RT + PBS (20 ml/kg/day); and iv) RT + SFI (20 ml/kg/day). SFI and PBS were administered via intraperitoneal injection 1 week before and 2 weeks after RT. The pathology of RILI and any clinical signs of toxicity were monitored. The expression of tumour necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 in the lungs was analyzed by RT-PCR and immunohistochemistry. TNF-α and TGF-β1 expression was increased by RT, but was reversed by SFI treatment during the radiation pneumonic and fibrotic phases (P<0.05). Lung histology at 24 weeks revealed a significant decrease in structural damage and collagen deposition in the RT + SFI group compared to the RT + PBS group. In conclusion, TNF-α and TGF-β1 are key mediators for the pathogenesis of RILI, and SFI reduces TNF-α and TGF-β1 expression after RT. This may be a key mechanism behind the preventive effects of SFI on lung injury after radiation.