Background: Oral lichen planus (OLP) is a T-cell-mediated disorder of oral mucosa and is mainly observed in middle-aged adult women. The etiology of OLP is unclear. Objective: This study investigates the potential role of serotonin in the pathogenesis of OLP, thourgh evaluation of the immunohistochemical expression of serotonin (5-HT) in biopsies from patients with OLP and its association with clinicopathological findings. /Patients and methods: Paraffin-embedded tissue samples were histologically confirmed as OLP. Monoclonal antibody serotonin was used for immunohistochemical staining. The patterns of positively stained cells were analyzed using semiquantitative techniques. Results: A total 40 biopsies from 24 female and 16 male OLP patients were involved. The mean age was 49.15 (SD 11.39) years. Using an immunohistochemical method, the results showed that the intensity of expression of 5-HT   at the basal layer was established in 11 (27.5%) cases who had grade 0, 18 (45%) cases had grade 1, and 11 (27.5%) cases had grade 2, with a median H-index of 55 ranging between 0-200. The intensity of 5-HT expression at the suprabasal layer showed that 7 (17.5%) cases had grade 0, 15 (37.5%) cases had intensity grade 1, 16 (40%) cases had intensity grade 2, and only two (5%) cases had grade 3, with a median H-index was 80, ranging between 0-300. The median total H-index was 153.5 (SD 111.5), ranging between 0-500. Conclusions: Serotonin has been proven in the epithelium of oral lichen planus in most studied cases, which is considered an important marker in its pathogenesis.