Background: Despite exhaustive research, melanocyte disappearance and the evolution of vitiligo remain enigmatic, and although multi-factorial, oxidative stress appears as a major player. The role of cutaneous cholinergic system in vitiligo pathogenesis has also been reported in some studies.Objective: To evaluate and correlate the influence of phototherapy on cutaneous cholinergic system and oxidative stress in vitiligo.Methods: Acetyl choline (ACh), its receptors; nicotinic (nAChR) and muscarinic (mAChR); acetylcholine esterase (AChE) and H 2 O 2 levels were estimated in de-pigmented and re-pigmented lesions of 30 vitiligo patients before and after NB-UVB phototherapy and in 30 controls. ACh and H 2 O 2 levels were measured by colorimetry. AChE and acetylcholine receptors expression were measured by quantitative real-time PCR.Results: Mean ACh and H 2 O 2 levels were significantly higher in vitiligo lesions before NB-UVB (P < .001) whereas AChE enzyme level was significantly lower (P < .001) compared to both re-pigmented and control skin. Additionally, mean mAChR was significantly higher and mean nAChR was significantly lower in vitiligo lesions before NB-UVB versus controls and re-pigmented skin (P < .001). Also, H 2 O 2 and AChE showed negative correlation whereas ACh and mAChR showed significant positive correlation. Although all the studied parameters showed significant changes after treatment and subsequent re-pigmentation, a significant difference continued to exist between all vitiligo skin and controls. Conclusion:Cholinergic system is strongly involved in vitiligo pathogenesis through H 2 O 2 inhibition of AChE which could be reversed by NB-UVB. Moreover, the strong activation of mAChRs may reflect genetic and/or acquired errors, direct up-regulation by ACh and H 2 O 2 or both. K E Y W O R D S acetyl choline, acetyl choline esterase, acetyl choline receptors, hydrogen peroxide, NB-UVB | 307 SAID et Al. How to cite this article: Said ER, Nagui NAER, Rashed LA, Mostafa WZ. Oxidative stress and the cholinergic system in non-segmental vitiligo: Effect of narrow band ultraviolet b.