Pulmonary fibrosis is a common delayed side effect of radiation therapy. Since its mechanism is almost unknown, little can be done to prevent or treat it. Th2 cytokines have been clearly implicated as mediators of asthma, and evidence is mounting that type 2 immune responses may also promote the development of pulmonary fibrosis. The aim of this study was to investigate whether Th2-like immune responses account for the development and progression of chronic radiation pulmonary fibrosis. C57BL/6 mice received thoracic irradiation of 12 Gy and were sacrificed at 1 h and 1, 2, 4, 8, 16 and 24 weeks post-irradiation (p.i.). We assayed the expression of IL-13 in serum, and the expression of hydroxyproline and the mRNA and protein of GATA-3 and Arg-1 in lung tissue. mRNA and protein analysis revealed the expression of these Th2-immune response-associated factors (GATA-3, IL-13 and Arg-1) in mice after irradiation. Without causing conspicuous fibrotic pathological changes at the early post-irradiation phase (1 and 2 weeks p.i.), a Th2 profile was confirmed by significantly elevated expression of Th2-specific transcription factor GATA-3 mRNA (P<0.01). Protein analysis confirmed the GATA-3 mRNA expression. Following significantly elevated expression of hydroxyproline (P<0.01) at 16 weeks p.i., IL-13 and Arg-1 expression reached maximal values in serum and lung tissue and maintained high levels up to 24 weeks p.i., respectively (P<0.01). Our data indicate that lung irradiation induces Th2 polarization. Furthermore, Th2-like immune response may take part in radiation-induced pulmonary fibrosis (RILF), and GATA-3 may play an important role in promoting RILF. Thus, GATA-3 may be an important target for the treatment of RILF.