Systemic sclerosis (SSc), also known as scleroderma, is a rare autoimmune connective tissue disorder associated with significant morbidity and mortality. Numerous studies have reported the involvement of the immune system, particularly T, B, and NK cell-mediated responses, in SSc pathogenesis. However, the underlying mechanisms remain elusive. Therefore, the development of a humanized immune system reconstitution mouse model is essential for advancing such investigations. In this study, we utilized Bleomycin (BLM) to induce a scleroderma mouse model in HSC-NCG-IL15 mice.