Objective To investigate the role of atrial natriuretic peptide (ANP) in lung metastasis of melanoma. Methods Melanoma B16F10 cells were intravenously injected into ANP knockout mice and C57BL/6J mice. After threeweeks, the mice were sacrificed, and the lungs were removed, embedded, and examined by pathology using HE staining. The numbers of metastatic foci on the lung surface and micrometastatic foci in the lung tissues were counted. Results The ANP knockout mice displayed fewer metastatic foci on the lung surface and less micrometastatic foci in the lung tissues of ANP knockout mice than in the C57BL/6J mice. Conclusions ANP deletion significantly suppresses the metastasis of melanoma in the lung of mice.