Background: Psoriasis is a chronic relapsing, immunemediated inflammatory skin disease of unknown etiology. The role of thrombomodulin (TM) in different autoimmune inflammatory diseases was explored previously in some studies. Thus; the aim of this study was to assess TM expression in the affected skin of patients with psoriasis. Methods: This prospective case-control study was carried out on 30 patients with chronic plaque psoriasis and 30 age and gender matched apparently normal subjects as a control group. Skin biopsies were taken for immunohistochemical evaluation of TM expression. Results: There was a highly significant difference between the two studied groups regarding the expression of TM in the skin. Patients group had a higher expression of TM in both epidermis and dermis compared to controls with a highly statistically significant difference, P-value< 0.01. Conclusions: These findings might provide a new sight of psoriasis pathogenesis in which TM appears to be implicated but its specific function remains unclear. Therefore, further studies are required to indicate the role of the TM in the pathogenesis of psoriasis and resolve the controversy about TM expression in the disease.