Objective To study the tumorigenesis and metastasis of Lewis lung cancer derived from lung metastases in C57BL/ 6 mice. Methods Lewis lung cancer tumor-bearing mice with lung metastasis were dissected, and lung metastases were isolated to prepare a cell suspension, which was inoculated subcutaneously into the axilla of the right forelimbs of C57BL/ 6 mice. A mouse model of Lewis lung cancer derived from lung metastases was established and designated as the lung tumor group. Subcutaneously transplanted tumor passaged mice were used as the subcutaneous group. The tumor diameter of mice was measured periodically, the tumor volume was calculated, and a survival curve was drawn. Anatomical observation was performed on lung and liver lesions, and HE staining was used to detect pathological changes in the lungs and liver. The ultrastructure of tumor cells was observed by transmission electron microscopy. Results The tumor volume of the lung tumor group was less than that of the subcutaneous group(P>0. 05). The survival rate of the lung tumor group was higher than that of the subcutaneous group during the observation period. Anatomic observation showed the lung and liver metastasis rates to be 37. 5% and 25% in the lung tumor group and 20% and no liver metostasis in the subcutaneous group, respectively. In HE staining, lung and liver metastases in the lung tumor group were large,darkly stained, approximately round in appearance, and demarcation from surrounding tissues was obvious. Lung metastases in subcutaneous group were small, and no typical liver metastases were seen. Tumor cells in the metastases showed typical bizarre nuclei and pathological mitosis under transmission electron microscopy. Conclusions Compared with subcutaneous tumor mice, lung tumor mice showed slower tumor growth, a higher survival rate within the same observation period, and stronger distant metastatic properties.