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Objective: To establish a nude mice model of human osteosarcoma lung metastasis. Methods: The growth of human osteosarcoma cell sublines M8 and M6 was determined by MTT assay. 2 × 107 cells were injected into the tail vein of nude mice. Mice were sacrificed started on week 4 after injection, and lung metastases were evaluated under both macroscopic and microscopic observation with HE staining. Results: The growth of low-metastatic subline M6 was lower than high-metastatic sublines M8. Seventeen mice after injected M8 had occurred lung metastases while only one mice had occurred in M6 group. Moreover, M8 cells within metastases were arrangement disorder with variable nuclear hyperchromasia.Conclusion: A mouse model for human osteosarcoma cancer lung metastasis can be established by injection different ability of metastasis MG63 cells into tail vein.