Aplastic Anemia (AA) is a syndrome of bone marrow hematopoietic failure manifested also by pancytopenia, hemorrhage, and infection. The pathogenesis of AA involves Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs), which are key components of the bone marrow hematopoietic microenvironment and hematopoietic regulation. Abnormal activation of the immune system plays an important role in the pathogenesis of aplastic anemia. The immunosuppressant Cyclosporine (CsA) is widely used to treat AA, but its effect on BM-MSCs remains unclear. In this study, the effects of CsA on proliferation, apoptosis, morphology, matrilineage differentiation and immune regulation of BM-MSCs in AA patients were verified. Our results show that CsA regulates the bone marrow microenvironment in AA by reducing BM-MSCs adipogenic differentiation through the transforming growth factor beta 1 signaling pathway. Meanwhile, CsA can upregulate the expression levels of PD-L1 and PD-L2, especially PD-L1 positive cells, by transforming growth factor beta secretion and/or reducing the levels of IL6, further enhance the immunosuppressive ability of BM-MSCs which is beneficial for treating AA.