Oral lichen planus (OLP) is a common, chronic relapsing inflammatory disorder of the mucous membranes, which causes major discomfort. Current treatment includes topical/systemic glucocorticoids, immune modulators and systemic immunosuppressants, which may lead to considerable side-effects. The aim of this study was to determine the clinical and immunological efficacy of photodynamic therapy (PDT) in OLP as an alternative, easy-to-use, safe and non-invasive treatment. Twenty patients with OLP were treated with PDT in a prospective case-controlled pilot-study. PDT was performed on the most extensive oral lesion in 4 sessions (day 1, 3, 7, 14). Peripheral blood and lesional T cells were analysed before (day 1) and after PDT treatment (day 28). PDT led to a statistically significant reduction of clinical parameters (lesion size, ABSIS, Thongprasom-score) and improvement of all evaluated quality-of-life (QOL) items. The clinical improvement was accompanied by a significant decrease of the relative number of CD4+ and CD8+ T cells in mucosal OLP-lesions. Furthermore, CXCL10 plasma levels were decreased and the number of activated peripheral CD4 + CD137+ and CD8 + CD137+ T cells and IL-17-secreting T cells was diminished. PDT treatment in OLP leads to lesion reduction and improvement of QOL, and induces local and systemic anti-inflammatory effects. The study identifies PDT as a novel therapeutic option in OLP. Lichen planus (LP) is a common T cell mediated, chronic inflammatory disorder which affects the oral mucosa and causes major discomfort, its etiology is still not entirely elucidated 1-4. Oral LP (OLP) affects the buccal mucosa, tongue and gingiva, and usually presents with symmetrical, bilateral or multiple lesions 5,6. The erosive and atrophic forms may present with remarkable burning and pain sensations that restrict food intake and performance of oral hygiene measures leading to weight loss, nutritional deficiencies 7,8 , loss of teeth and function with a major impact on the quality of life (QOL). These OLP forms are often resistant to treatment 9,10 and have a higher tendency to malignant transformation 11,12. At present, topical corticosteroids are widely accepted as the primary choice of OLP therapy, but other therapeutical protocols have also been investigated, i.e. topical and systemic retinoids, calcineurin inhibitors, aloe-vera, and thalidomide 6,7,13-25. However, some of these treatment options proved to be ineffective or only partially effective 12. Photodynamic therapy (PDT) as an easy-to-use and safe treatment option induces cell and tissue damage by combining the use of a photosensitizer and light that activates the photosensitizer by exposure to low-level visible light in an appropriate wavelength. The general principle of PDT was first described in 1900 by the work of Raab and Tappeiner who evaluated the effects of acridine on malaria-causing protozoa showing a lethal effect of this combination on a species of paramecium (Infusoria) 26. They discovered the optical property of fluorescence and that...