Introduction: Regular physical exercise provides a significant risk reduction for breast cancer and recent studies suggest beneficial effects also on disease specific recurrence and mortality. However, little is known about how exercise exerts its protective effects. Aim; to evaluate the effect of voluntary running on tumor progression and metastasis in the PyMT mouse model of breast cancer. Methods: From 4 weeks of age, female MMTV-PyMT mice on the FVB background were housed with access either to wirelessly recording running wheels or locked control wheels. Tumor growth was monitored continuously, tumor stage and pulmonary metastases were determined histologically at the 12 week endpoint. In a follow up study, pre-trained female FVB mice were injected intravenously with 2*105 PyMT derived tumor cells (IC3) and after an additional 10 weeks of voluntary running, pulmonary metastases and immune cell infiltration was quantified (histologically and with flow cytometry). The CD8+ T-cell population was deleted using weekly administration of CD8 specific antibodies. Results: PyMT mice average running distance was 6.4±2.4 km/day. No significant effects of voluntary running on tumor- initiation, volume or stage were found. However, a reduced number of metastases were observed in mice with access to running wheels (Ctrl 22.0±6.8 and Runners 9.1±1.7). Significant reductions in pulmonary metastasis frequency were also found in runners after intravenous injections of tumor cells (Ctrl 5.2±1.1 and Runners 1.9±0.7) and running mice had a lower number of metastases with a high proliferation score. Metastatic lesions from running mice showed higher content of Granzyme B positive cells (Ctrl 1.2±0.5 and Runners 4.9±1.1), indicating an increased infiltration of cytotoxic T-cells. Depletion of CD8+ cells abolished the reduction in metastatic burden found in running mice compared to non-running mice All data is presented as Mean±SEM. Discussion: In this highly aggressive, genetic, breast cancer model, an average of 6 km/day of voluntary running showed little effect on tumor formation and growth. However, the findings suggest that physical activity reduced outgrowth of metastatic lesions through an increased infiltration of cytotoxic immune cells.