Background: Vitiligo is a commonly acquired depigmentation disorder of the skin, related to the loss of functioning melanocytes or melanin in the epidermis or mucosa, or/and hair folliculi. Interleukin-33 (IL-33), a member of IL-1 family, has been reported to acts as an alarmin because of its release after necrosis or tissue damage. Objectives: to evaluate whether serum levels of IL-33 is increased in vitiligo patients, and evaluate its relation with disease severity. Methods: A case-control study included 44 subjects who were divided into two groups; Group A: included 22 vitiligo patients (15 males, 7 females) with age ranging from 7-62 years old. Severity of vitiligo was assesed by VASI score. Group B: included 22 apparently healthy persons (17 males, 5 females) with age ranging from 15-60 years old. Serum IL- 33 level was measured by ELIZA in both vitiligo and control group. Results: Serum IL-33 levels were significantly higher in vitiligo patients than control group and its level was significantly related to disease severity measured by VASI score. There was no significant correlation between gender, age, duration of the disease or family history and serum IL-33 levels. Conclusion: IL-33 may have an important role in the pathogenesis of vitiligo.