Background: Lichen planus disease is a chronic inflammatory disorder of mucosal and cutaneous tissues, and its etiology and pathogenesis are unclear. Cytokines have a significant role in the beginning, the maintenance of inflammatory and intercellular crosstalk. Aim: We assessed serum levels of neutrophil activation marker (calprotectin) in patients with cutaneous lichen planus with different subtypes and made a comparison with healthy individuals. Materials and Method: Peripheral blood samples of 30 cases with lichen planus were compared with 30 healthy individuals. Serum samples were prepared from LP patients, using a commercial ELISA kit, and calprotectin level was measured in each serum sample. Results: The serum level of calprotectin was significantly raised in LP cases compared with control (141.34 ± 17.47 ng/ml versus 40.03 ± 1.54 ng/ml respectively; p < 0.001). No correlation was recorded among of serum of calprotectin and patients’ ages, sex, disease period, and the existence or strength of pruritus. But a strong positive correlation was present between the coexistence of oral lesions and the number of locations. Conclusion: Calprotectin can be used as a marker of Lichen planus severity and progression. Calprotectin may play a role in the pathogenesis of LP.