Background: Exercise is established as a treatment option in PAD, even though the molecular mechanisms are not yet fully understood. An animal model was developed to evaluate collateral growth through exercise. Methods: 12 weeks old healthy C57BL/6 mice were compared to 18 wk. old ApoE-/- deficient mice, showing after 12 wk. of high caloric diet cardiovascular deficits. Ligation of the superficial femoral artery simulated acute limb occlusion. Both groups where exposed to freely accessible running wheels to evaluate training effects and in motion-restricting cages as control baseline. Hind limb perfusion was measured by LDPI pre- and postoperative at different points in time. At each of these points body weight was recorded as well as histological/morphometric Mm. adductores examinations were performed. Results: ApoE-/- mice showed significant macroscopic arteriosclerotic changes and an increase in body weight compared to BL6, but no differences of distances were observed. LDPI on BL6 did not show differences between training and resting. There was a continuous improvement in reperfusion to d14 to stabilize at 70% of baseline. ApoE showed significant differences between training and control on d7 on which this reperfusion stabilized at 70% of baseline. It was shown that there is a difference (p<0,05) of perfusion between the animal strains immediately postoperative as well as on d3 and d7. There is no difference in size of collateral arteries between the groups. A significant increase of macrophages and a higher endothelial monocyte activity can be seen in the first week in ApoE mice with training. Conclusion: The running wheels were accepted by both groups. Due to pre-existing cardiovascular deficiencies ApoE-/- mice were proven to be a suitable model to picture PAD. It was shown there is evidence that exercise significantly accelerates reperfusion through collateral growth, an increased endothelial proliferation activity and a higher accumulation of macrophages due to training.