Background: Lichen planus is a common chronic cutaneous inflammatory disease. Recent advances evidenced that angiogenesis is tightly connected to it. More recently, the endothelial specific growth factor angiopoietin-2 has been clarified to interact with vascular endothelial growth factor. Angiopoietin-2 level has not been investigated in lichen planus. Aim: To evaluate serum level of angiopoietin-2 in cutaneous and oral lichen planus. Methods: Ninety patients were investigated, 45 patients with lichen planus. In addition to forty-five healthy control, the activity of the disease was estimated at the time of examination. The serum level of angiopoietin-2 had been estimated by enzyme-linked immunosorbent assay. The relationships between angiopoietin-2 serum level and disease severity, type of lichen, and visual analogue scale score (VAS) were determined. Results: The serum levels of angiopoietin-2 were substantially higher in patients with both cutaneous and oral lesions than patients with cutaneous lichen planus only (P < .001). Conclusions: Serum angiopoietin-2 is elevated in patients compared with normal subjects and is correlated with the presence of oral lesions and disease severity, that reflects its role in angiogenesis and inflammation, and angiopoietin-2 serum level could be a potential marker for monitoring the oral lichen to identify possible malignant transformation.