Background: Vitiligo is a multifactorial disorder that associated with the destruction of melanocytes resulting from immune and inflammatory mediators. The most important theory about the pathogenesis of vitiligo is the autoimmune theory in which cytokines and inflammatory mediators such as GM-CSF, TNFα, IL6, IL1 and IL8 play a key role. YKL-40 is one of the major secreted proteins from human articular chondrocytes, synovial cells, endothelial cells and macrophages, and expressed by mature neutrophils.It is suggested that it participates in many physiological and pathological processes such as proliferation, angiogenesis, mitogenesis and remodelling. C-reactive protein is an acute phase protein secreted in the blood stream by the liver in response to inflammatory cytokines such as IL6 and several other systemic inflammation biomarkers. ESR is routinely measured in clinical practice, as an indicator of infection, sepsis, or autoimmunity and malignancy. The aim of this study was to evaluate serum level of YKL-40, hs-CRP and ESR in vitiligo patients in comparison with normal controls. Methods: This study included 40 vitiligo patients, and 40 apparently healthy volunteers who served as controls. The patients were recruited from the outpatient clinic of Dermatology and Andrology Department of Benha University Hospitals. Results: Regarding the course of vitiligo ,92.5% of the studied cases had active disease. The most common sites of vitiligo were upper limb, face and lower limb and 45% of the cases had lesions in two sites. The serum level of YKL-40, hs-CRP and ESR were significantly higher in vitiligo patients compared to control. Conclusion: This study showed that YKL-40, hs-CRP and ESR levels were elevated in vitiligo patients. Thus, there is a relation between vitiligo and inflammation. From the results of the present study, it is concluded that serum YKL-40 may play a role in vitiligo pathogenesis.