Background: Vitiligo is a disorder characterised by depigmented patches in the skin due to partial or complete loss of melanocytes. Proopiomelanocortin (POMC) and melanocortin 1 receptor (MC1R) are important regulators of melanogenesis and pigmentation. The possible role of the melanocortin system in the pathogenesis of vitiligo remains unclear. Aim of the work: The aim of this study was to examine the expression of POMC and MC1R in lesional and non lesional skin of vitiligo patients and in skin of healthy controls in order to verify their possible role in the pathogenesis of vitiligo.Patient and Methods: The present study included 20 vitiligo patients and 20 healthy controls. Skin biopsies were taken from lesional and non lesional skin of vitiligo patients and from non-sun exposed skin of healthy controls to examine the expression of POMC and MC1R using quantitative real time polymerase chain reaction technique.Results: POMC and MC1R expressions were significantly lower in lesional skin compared to controls (p=0.000) and significantly higher in non lesional skin compared to controls (p=0.000). In addition, the 2 studied parameters were significantly lower in lesional skin than in non lesional skin of vitiligo patients (p=0.000). There was a statistically highly significant positive correlation between lesional levels of POMC and MC1R, as well as between non lesional levels of POMC and MC1R. In addition, a statistically significant negative correlation was detected between the lesional and non lesional levels of POMC, as well as between the lesional and the non lesional levels of MC1R.Conclusion: The present study demonstrated significantly lower POMC and MC1R expressions in lesional skin of vitiligo patients and significantly higher expressions in non lesional skin, both compared to controls, as well as significantly lower expressions in lesional than non lesional skin, suggesting a role for their deficiency in the pathogenesis of vitiligo and a compensatory increase in non lesional skin to restore defective pigmentation.