Objective To establish an optimal animal model of pulmonary metastasis of human lung adenocarcinoma, to serve further investigation of mechanism of lung adenocarcinoma metastasis. Methods Eleven nude mice aged 4-6 weeks were used in this study. Suspension of human lung adnocarcinoma A549 cells (0.1 mL, 10⁷ cells/mL) was injected into the tail vein in nude mice. From four weeks after inoculation, two nude mice were killed each time at 4, 5, 6 weeks after the tumor cell injection at random for examination. The remaining 3 mice were killed at the end of the experiment. At autopsy, the lung, brain, liver, kidney and other organs were removed, fixed in neutral buffered formalin and embedded in paraffin. Sections were cut and stained with hematoxylin-eosin, and examined by histopathology. The number of metastatic foci was counted. Results No mouse died after tumor cell inoculation. Serially euthanized mice revealed evidence of gradually increasing pulmonary metastases in the mice: No metastasis was found before 4 weeks after tumor cell inoculation, the first histological metastases appeared at 5 weeks, gross metastatic foci were observed at 6 weeks, widely spread metastatic foci were observed at 7 weeks, and the remain 3 mice developed cachesia at 11, 13, and 14 weeks after tumor cell inoculation. Mediastinal lymph node metastases were found in the nude mice by 11 weeks after tumor cell inoculation. Conclusions We have successfully established a nude mouse model of pulmonary metastasis by injecting human lung adenocarcinoma A549 cells into the tail vein.