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Leprosy is an infectious disease caused by non‐cultivable bacteria Mycobacterium leprae. Th17 cells play vital roles during pathogenesis of leprosy reactions and IL‐23 is involved in Th17 cell differentiation. Although previous studies have reported the participation of IL‐23 in leprosy patients in peripheral blood, the role of this cytokine in skin has not yet been described for the disease. In this study, we first evaluated IL‐23 expression in the skin of patients with leprosy. Data showed that in keratinocytes, endothelial cells, and macrophages, IL‐23 expression was markedly higher in patients compared to that in the normal skin controls. Also, leprosy patients presented higher percentage of IL‐17A‐producing IL‐23R + CD4 T cells than healthy donors. IL‐23R blocking induced markedly downregulated IL‐17A secretion in leprosy patients but not in healthy donors. Furthermore, TGF‐β expression was significantly elevated after IL‐23R blocking. Overall, this study establishes that Th17 cells produce IL‐17A in an IL‐23 dependent manner in the skin of leprosy patients and provides more focused treatment strategies for Mycobacterium leprae. [ABSTRACT FROM AUTHOR]