Radiotherapy is one of the conventional treatments for head and neck malignancies. Despite the implementation of protective measures to minimize the detrimental impact on healthy tissues surrounding the radiation site, radiation keratopathy remains a prevalent complication. We aimed to establish a mouse model of radiation keratopathy to characterize the pathophysiology of the disease and enable future identification of potential treatments. Thirty-six mice were divided equally into six groups. One eye of each mouse was irradiated with 5, 10, 15, 20, 25, and 30 Gy and the other eye used as a control. The mice were clinically monitored for one year, at which time eyes were tested using anterior segment optical coherence tomography, then the mice were euthanized, and the corneas dissected. Corneal sections were stained with hematoxylin and eosin, β-galactosidase, and CK12. The results indicated that animals experiencing increased doses of radiation had increased corneal vascularization, fibrosis, and opacity and conjuctivalization and a higher number of positive results of beta-galactosidase staining, which indicates an increase in the tendency of senescence. The results of β-III tubulin staining indicated that the density of corneal stromal nerves and the subepithelial nerve plexus decreases as the dose increases. Also, as the irradiation dose increases, the central corneal thickness decreases as well.