Background: Vitiligo is a skin disease with complex, multifactorial pathogenesis. Abnormalities in surrounding keratinocytes may cause melanocyte death due to deprivation of growth factors. Narrow band ultraviolet B (NB-UVB) is an effective therapeutic option especially in patients with generalized disease. Objective: The aim of this study was to identify histopathological changes in lesional and perilesional skin of vitiligo patients and the effect of NB-UVB therapy on them. Methods: Twenty patients were enrolled in this study. They received NB-UVB twice weekly on non-consecutive days for a total of 40 sessions. Skin biopsies from lesional and perilesional skin were obtained from each patient before and after therapy. Results: After therapy, 10% of patients showed excellent clinical response, 10% showed good response, 40% showed moderate response, 35% showed poor response and 5% showed progressive disease. Before therapy, 50% of patients showed a basal lymphocytic infiltrate with a perivascular lymphocytic infiltrate in both lesional and perilesional skin. 40% of them showed additional hydropic degeneration of lower epidermis with apoptotic keratinocytes in 20% of them. After therapy, these inflammatory changes were significantly reduced (p=0.04). Conclusion: NB-UVB is an effective method of treatment of vitiligo. This may be due to its immunosuppressive effects. Also, keratinocyte apoptosis may have a role in pathogenesis of vitiligo.