Objective To investigate the potential of chronic myeloid leukemia (CML) cell line KCL22 in inducing leukemia in NOD-SCID mice for setting up a basis for constructing a CML mouse transplantation tumor model. Methods 2×10⁷ KCL22 cells in logarithmic growth phase were injected via the tail vein into experimental NOD-SCID mice whereas PBS was injected to the mice of control group. General condition of the mice of both groups was observed. Wright staining was used to observe the changes of blood and bone marrow smears. PCR was conducted to detect the transcription level of BCR-ABL, and histology with HE staining was used to evaluate the tumor cell invasion in the liver and spleen. Results Four weeks after the injection of KCL22 cells, the mice in experimental group showed physical signs of decreased reactivity, depression, swollen hindlimb muscles and petechia on the hindlimb femur. Peripheral white blood cells (WBC) began to increase after 5 weeks, with a significantly increased quantity compared with the control group (P<0.05). Immature granulocytes could be seen in blood and bone marrow smears, and tumor cell infiltration was found in the liver and spleen. BCR-ABL was highly expressed in bone marrow cells. Survival time of the experimental mice without therapy was 70 days, significantly shorter than that in the control group (>90 days) (P<0.05). Conclusions A NOD-SCID mouse model of CML transplantation tumor is successfully established with leukemia KCL22 cells.