Objective To explore the role and possible mechanism of CD28/B7 molecules in T cell ab-normal activation by establishing a mouse model of the autoimmune aplastic anemia. Methods Unmanipulated B6D2F1 or CByB6F1 hybrid mice were infused with about 40 × 106 lymph node (LN) cells from their C57BL/6 (B6) parent. Distribution of the injected T cells was assayed by CFDA-SE fluorescent staining. Anti-D80 and anti-CD86 monoclonal antibodies were used to block CD28/B7 signal transduction pathways and to test the change of peripheral blood of F1 mice at different times. Damage was assessed by histological staining. Bone marrow (BM) cells and LN iymphocytes were cultured to observe the effect of different number of lymphocytes in the LN on BM cells' hematopoiesis by the count of hematopoietic colony-forming cells, and to test the effect of cyclosporine A of different concentration on BM cells' hematopoiesis. Results Infusion of about 40 × 106/mouse B6 LN cells led to the development of BM failure in the fifth day: anemia, neutropenia and thrombocytopenia. At 21st day recipients began to appear death. Frozen section revealed the injected lymph node major in myeloid tissue. Pathological sec-tion revealed obvious immune-induced marrow destruction and tissue destruction. There was similar performance of the above in the recipients infused with anti-D80 and anti-CD86 monoclonal antibodies. B6 LN five times the num-ber of lymphocytes in the blood cells F1, CFU-E and CFU-G colony formation of a blank group difference was not significant (P >0.05); When B6 LN 10 times the number of lymphocytes in the blood cells F1, CFU-E colony forming significantly reduce the number of (P < 0.05) ; When B6 LN lymphocytes 50 times in F1 hematopoietic cells, not observed CFU-E colony formation. CFU-E and CFU-G colony formation reducing the number of lympho-cytes showed a dose-dependent. Cyclosporine A can significantly increase the CFU-E and CFU-G colony forming rate. Conclusion This mouse model indicates that activated lymphocytes play important roles in marrow destruc-tion in lymphocyte infusion-induced BM failure. Only blocking the CD28/B7 signal transduction can not block the abnormal T-cells activated.