Objective To establish an endothelial conditional EMCN-knockout mouse model and explore the differences between tumor lung metastases in these and C57BL/ 6 mice. Methods Endothelial-cell-specific Tek-creERT2 mice were mated with EMCN^{flox / flox} mice. Male EMCN^{flox / wt} / Tek-CreERT2⁺ mice were crossed with female EMCN^{flox / flox} mice to acquire endothelial cell-specific EMCN-knockout mice ( EMCN^{flox / flox} / Tek-CreERT2⁺ , EMCN^ecko ). To verify the gene knockout accuracy and efficiency at the DNA and protein level, the genomic DNA of mice was extracted, and the Tek- creERT2 and Flox sites were detected by PCR amplification. After tamoxifen induction, expression of the EMCN protein was detected on Western Blot. The phenotypes of normal C57BL/ 6 mice and EMCN^ecko mice were observed, and the organs were stained with hematoxylin and eosin ( HE). To confirm the effect of EMCN knockout on tumor metastasis, ( Lewis lung carcinoma, LLC) LLC cells were intravenously injected into C57BL/ 6 and EMCN^ecko mice. After 2 weeks, the lungs were dissected to detect metastasis, and the result for the two groups of mice were compared and analyzed. LLC cells were subcutaneously injected into C57BL/ 6 and EMCN^ecko mice. The subcutaneous tumors were removed 2 weeks later, and lung metastasis was observed 2 and 3 weeks after the operation. The lung tissues were stained with HE, and the metastasis result of the two groups were compared and analyzed. Results We confirmed the successful construction of EMCN^{flox / flox} / Tek- CreERT2⁺ mice at the gene and protein level. Preliminary phenotypic analysis showed no abnormal organ development in the gene-knockout mice. C57BL/ 6 and EMCN^ecko mice given intravenous injection and tumor resection after subcutaneous injection can develop lung metastases. Compared with C57BL/ 6 mice, the deletion of endothelial cell EMCN expression significantly promoted lung metastasis. Conclusions Endothelial-cell-specific EMCN-knockout mice were successfully obtained. The frequency of lung metastasis in endothelial cell EMCN-knockout mice was significantly higher than that in normal C57BL/ 6 mice. This approach is expected to provide an efficient lung metastasis animal model for the study of tumor metastasis .