Pulmonary damage after radiotherapy is typically characterized by an initial alveolar inflammation (pneumonitis) followed by chronic fibrosis. In the present study, changes in lung architecture were measured in the pneumonitis phase after whole-body low-dose X irradiation of C57BL/6 mice. Radiation damage was evaluated at 24 h and 1–8 weeks postirradiation. Three distinct scoring systems were used: (1) manually evaluating alveolar distortion and infiltration of inflammatory cells into the alveolar space using a continuous numerical scale across an entire lung section, (2) physically measuring the average thickness of the alveolar septa from multiple representative microscope fields, and (3) a new rapid automated mathematical algorithm based on image segmentation of alveolar space across an entire section. Each scoring method detected significant changes in alveolar architecture at the earliest times compared with sham-treated controls and gave comparable evaluations of injury. The results from the automated mathematical algorithm correlated significantly with both the manual evaluation method (Spearman's correlation coefficient ρ  =  0.044) and the direct physical measurement of septa thickness (ρ  =  0.002). These data demonstrate that evaluating alveolar space by segmentation analysis provides a reliable method for scoring early pulmonary radiation damage that is consistent with more established methodologies but is more rapid and is independent of potential operator and selection bias.