Radiation-induced lung injury, including the acute pulmonary inflammation and chronic pulmonary fibrosis remains the major complication of thoracic radiotherapy.In this study, we assessed the effects of Ophiopogon japonicus (O. japonicas) in inhibiting the radiation-induced pulmonary inflammation through an acute lung injury mouse model using C57BL/6 mice that received 18 Gy irradiation to the thoracic region. Starting at 4 days before radiation, mice were treated with O. japonicus or dexamethasone combined with cephalexin or vehicle daily for 14 days.Exposure to radiation resulted in pulmonary inflammation in mice, but treatment with O. japonicus or dexamethasone-cephalexin could both significantly reduce radiation-induced pulmonary inflammation through inhibition of IL-6, TNF-α, TGF-β1, hydroxyproline, MDA, MMP-2 and TIMP-2 in plasma or lung tissue. In addition, through analyzing tissue damage, cytokines and inflammation-related protein at 12 weeks after irradiation, we found that the protective effect of O. japonicus was more enduring than dexamethasone-cephalexin.As radiation-induced lung injury is a major obstacle in thoracic radiotherapies and seriously affect the quality of patients' life. Application of O. japonicus may be a novel strategy to manage radiation-induced pulmonary inflammation.