Radiation‑induced lung injury (RILI) is a prevalent complication following thoracic radiation, and currently there is a lack of effective intervention options. The present study investigated the potential of Compound Kushen Injection (CKI), a botanical drug, to mitigate inflammatory responses in mice with RILI, along with its underlying mechanisms of action. C3H mice underwent total lung irradiation (TLI) and intraperitoneal injection of CKI (2, 4 or 8 ml/kg) once daily for 8 weeks. Pre‑radiation treatment with 4 or 8 ml/kg CKI starting 2 weeks before TLI or concurrent treatment of 8 ml/kg CKI with TLI led to a significantly longer overall survival compared with the TLI vehicle‑treated group. Micro‑computed tomography evaluations showed that concurrent treatment with 8 ml/kg CKI was associated with a significantly lower incidence of RILI. Histological evaluations revealed that concurrent CKI (4 and 8 ml/kg) treatment significantly reduced grades of lung inflammation. Following radiation at 72 h, TLI plus vehicle‑treated mice had significantly elevated serum IL6, IL17A, and transforming growth factor β (TGF‑β) levels compared with non‑irradiated normal mice. Conversely, mice that received TLI plus CKI displayed lower cytokine levels than those in the TLI plus vehicle‑treated mice. Immunohistochemistry staining showed a reduction of TGF‑β positive cells in the lung tissues of TLI mice after CKI treatment. The concurrent TLI CKI‑treated mice had a significantly reduced cyclooxygenase 2 (COX‑2) activity and COX‑2 metabolites compared with TLI vehicle‑treated mice. These data highlight that CKI substantially reduced radiation‑induced lung inflammation, mitigated RILI incidence, and prolonged overall survival.