Abstract: Objective：To establish a nude mouse model with metastatic human small cell lung cancer (SCLC) and explore the feasibility of the model used to study the treatment of human SCLC. Methods：Human SCLC cell line NCI-H446 was cultured in RPMI 1640 media and resuspended with free-serum media to prepare cell suspension with final concentration of 1×10⁷ cells/mL. The mouse model was established by injecting 0.1 mL of the cell suspension into the right proximal tibia of BALB/c-nu nude mouse and the growth and metastasis of the tumor in the nude mouse were observed. The expressions of both CD56, the specific marker of small cell lung cancer, and nestin, the marker of neuroepithelial stem cells, were detected by immunohistochemistry staining. Results：Orthotopic tumors in hind legs were produced successfully in all the nude mouse after NCI-H446 cells were injected, and the incidence of lung metastasis was 100%(6/6). Nevertheless, the metastasis of other organs e.g., liver, spleen, etc. was not found. The positive rates for CD56 and nestin in tumor cells were more than 75% and from 4% to 12%, respectively. Conclusion：The nude mouse model with metastatic human SCLC was established successfully by injecting lung cancer NCI-H446 cells into the tibia bone marrow of nude mouse, which provided an animal model for studying the treatment of human SCLC.