Vitiligo, an autoimmune disorder, is associated with altered cytokine levels and T lymphocytes. Lenalidomide modulates immune system components by altering cytokine production and regulating T-cell stimulation. In this study, effect of lenalidomide was checked on the development of vitiligo lesions, level of various cytokines, and T lymphocytes in the mouse model. The vitiligo mouse model was developed by immunizing C57BL/6 mouse with anti-mouse tyrosine-related protein 2. Lenalidomide was orally given to mice daily, and the effect was observed on the development of vitiligo lesions. The level of T lymphocytes in blood was checked by flow cytometry. Serum cytokine levels were checked by enzyme-linked immunosorbent assay. Vitiligo lesions were found significantly smaller in lenalidomide-treated mice models. It significantly decreased the serum levels of IFN-γ, TNF-α, IL-1β, and IL-6 but elevated the levels of IL-4 and IL-10. It non-significantly elevated CD4+/CD8+ T-cell ratio. Lenalidomide had an inhibitory effect on the development of vitiligo lesions in mice models by suppressing the serum level of pro-inflammatory cytokines and increasing anti-inflammatory cytokine levels. It modulated the immune response in vitiligo mice models toward an anti-inflammatory profile suggesting its use in the management of vitiligo.