Objective To screen and optimize the modeling condition for radiation-induced heart damage (RIHD) models characterized by inflammatory-fibrosis pathological injury. Methods The rats were irradiated with single whole-body X-ray to screen the maximal tolerated dose. Based on the screened whole-body dose, single local heart irradiation doses were used to screen the minimal X-ray dose which could induce the significant cardiac damage. And the RIHD rat model was established by exposure to the screened dose of X-ray. Tissue samples were harvested 1 day, 1 week, 2 weeks, 4 weeks and 6 weeks after irradiation. The cardiac pathological injury score, collagen volume fraction (CVF) in myocardial tissues by Masson staining, plasma myocardial enzyme level, and the expression of inflammatory and fibrosis factors in myocardial tissues were examined for evaluating the animal model. Results The tolerance dose of whole-body irradiation was lower than 16 Gy for rats. Local irradiation dose at least 25 Gy could induce RIHD in rats. The pathological injury score of myocardial tissues, CVF in myocardial tissues and creatine kinase isoenzyme MB (CK-MB) and cardiac troponin (cTn) in plasma were increased in the RIHD model rats. Inflammatory factors including nuclear factor (NF)-κB p65, NF-κB p50 and tumor necrosis factor α (TNF-α) in myocardial tissues were increased 1 day after irradiation in the RIHD rats and maintained high to the fourth week. The expression levels of fibrotic molecules transforming growth factor β1 (TGF-β1), collagen type Ⅰ (ColⅠ) and ColⅢ in myocardial tissues were increased gradually, and reached the peaks at week 4 after irradiation. Conclusion Stable RIHD rat model can be established by irradiating the precardiac region with 25 Gy X-ray. Pathological observation and CVF can dynamically reflect the early inflammatory changes and the progression of fibrosis in RIHD rats. The sustained high expression of NF-κB p65, NF-κB p50 and TNF-α at early stage and the progressive increases of TGF-β1, ColⅠand ColⅢ can be used to evaluate the acute inflammatory injury and delayed fibrosis in the RIHD inflammatory-fibrosis model.