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<h4>Background</h4>Inflammatory skin reactions and skin alterations are still a potential side effect in radiation therapy (RT), which also need attention for patients' health care.<h4>Method</h4>In a pre-clinical study we consider alterations in irradiated in-vitro skin models of epidermal and dermal layers. Typical dose regimes in radiation therapy are applied for irradiation. For non-invasive imaging and characterization optical coherence tomography (OCT) is used. Histological staining method is additionally applied for comparison and discussion.<h4>Results</h4>Structural features, such as keratinization, modifications in epidermal cell layer thickness and disorder in the layering-as indications for reactions to ionizing radiation and aging-could be observed by means of OCT and confirmed by histology. We were able to recognize known RT induced changes such as hyper-keratosis, acantholysis, and epidermal hyperplasia as well as disruption and/or demarcation of the dermo-epidermal junction.<h4>Conclusion</h4>The results may pave the way for OCT to be considered as a possible adjunctive tool to detect and monitor early skin inflammation and side effects of radiotherapy, thus supporting patient healthcare in the future.