Abstract Purpose: RIHD is a serious complication of radiotherapy and a major contributor to non-cancer mortality. This study employs single-cell RNA sequencing (scRNA-seq) technology to investigate the dynamic immune landscape following radiation-induced cardiac injury, uncovering potential mechanisms of RIHD and providing strategies for its prevention and treatment. Methods: We constructed a single-cell immune atlas of the dynamic changes in cardiac injury after radiation, with a focus on the alterations and functional shifts in immune cells. Results: We identified nine immune cell types, totaling 24,683 leukocytes. Macrophages accounted for the largest proportion (78.45%). Over time following irradiation, the proportion of macrophages decreased, while monocytes, T cells, and dendritic cells (DCs) increased. B cells and natural killer (NK) cells showed a slight decrease on day 7 but peaked on day 35. Neutrophils reached their highest levels on day 7. We observed a significant increase in pro-inflammatory subpopulations on day 7 post-irradiation, along with elevated expression of pro-inflammatory genes. By day 35, the proportions of apoptosis- and proliferation-related subpopulations had significantly risen, with corresponding upregulation of apoptosis- and proliferation-related genes.We also observed two specific subpopulations: IFN+ macrophages and mregDCs.We identified a fibrosis-associated macrophage subpopulation: MHCII+_Ccr2 macrophages, and found that the SPP1 pathway was significantly expressed in this subpopulation 7 days post-irradiation. We further hypothesize that the SPP1-CD44 pathway may be closely associated with cardiac fibrosis. Conclusion: This study provides a comprehensive immune atlas of the mouse heart post-irradiation, revealing significant shifts in immune responses at different time points.