TGF-β is a pleiotropic cytokine that deploys several functions on different types of cells. In the lepromatous (LL) form of Leprosy, there is predominance of M2 macrophages, which induce the production of growth factors, such as TGF-β which is important for the mechanisms that cause apoptosis and healing. To study the immunoexpression of TGF-β in Hansen’s disease and to assess the severity of infection with potential response to treatment. The present study was carried out in 45 patients of Hansen’s disease after a detailed history and thorough physical examination performed in every subject and punch biopsies were performed. The specimens were fixed, paraffin embedded and sections of 3-5 microns thickness were cut and stained with hematoxylin and eosin stains. Additional sections of 3-4 microns thickness were cut and immunohistochemical staining by TGF-β antibody was performed. Of the 45 cases of Hansen’s disease, most of the cases were of Borderline Tuberculoid and Borderline Lepromatous, constituting 14 (31.1%) cases each, followed by 9 (20.0%) cases of Lepromatous Leprosy. Maximum cases, 12 (26.7%) each with intense reaction were of Borderline Tuberculoid and Borderline Lepromatous, followed by 6 (13.3%) cases of Lepromatous Leprosy. Most of the cases, 9 (20.0%) were of Borderline Lepromatous category with highest proportion score, followed by 7 cases (15.6%) of Borderline Tuberculoid. Highest number of cases, 9 (20.0%) with high immunoreactivity score were in Borderline Lepromatous, whereas most of the cases, 7(15.6%) with low immunoreactivity score were in Borderline Tuberculoid. The immunoexpression of TGF-β was more intense in lepromatous side of the spectrum as compared to the tuberculoid, which indicates the severity of the disease with less cure potential.