The present study assessed the effects of dietary fat on spontaneous metastasis of Lewis lung carcinoma in mice. Three-week old male C57BL/6 mice were fed the AIN-93G diet or a 45% fat diet (% kcal.) for 7 weeks before they were subcutaneously injected with 2.5 × 10⁵ viable carcinoma cells. The primary tumor was resected 2 weeks later, and mice were maintained on their respective diets for an additional 2 weeks. The high-fat diet significantly increased body weight and abdominal adipose weight compared to the AIN-93G diet. Feeding mice the 45% fat diet resulted in a two-fold increase in the number of lung metastases (P < 0.05), a 35% increase in tumor cross-sectional area, and a 50% increase in tumor volume compared to mice fed the AIN-93G diet. There were no differences in plasma concentrations of TIMP-1, IL-1β, VEGF and MCP-1 in non-tumor-bearing mice fed the AIN-93G diet or the high-fat diet, but significant increases in these cytokines in tumor-bearing mice fed the AIN-93G diet compared to the non-tumor-bearing mice fed the same diet (P < 0.05 for each comparison). Further significant increases in these cytokines in tumor-bearing mice fed the 45% fat diet compared to the same tumor-bearing mice fed the AIN-93G diet (P < 0.05 for each comparison). The high-fat diet significantly increased plasma leptin and significantly decreased plasma adiponectin compared to the AIN-93G diet in both non-tumor-bearing and tumor-bearing mice. Results of the present study demonstrated that the high-fat diet enhanced spontaneous metastasis of Lewis lung carcinoma in mice and that this aggressiveness was accompanied with significant increases in plasma concentrations of angiogenic cytokines, suggesting that dietary fat affects metastasis by promoting angiogenic processes.