G-CSF has been shown to improve cardiac function after myocardial infarction (MI) by bone marrow cell mobilization and by protecting cardiomyocytes from apoptotic cell death. However, its role in arteriogenesis has not been elucidated. Here, we investigated the effect of G-CSF on arteriolar growth and cardiac function in a murine MI model. Mice were treated with G-CSF (100mug/kg/d) after MI for 5 days. G-CSF application resulted in a significant increase of circulating mononuclear cells expressing stem cell markers. Arterioles in the border zone of infarcted myocardium showed an increased expression of ICAM-1 accompanied by an accumulation of bone marrow derived cells and a pronounced proliferation of endothelial and smooth muscle cells. Histology of G-CSF treated mice revealed a lower amount of granulation tissue (67.8% vs. 84.4%) associated with a subsequent reduction in free LV wall thinning and scar extension (23.1% vs. 30.8% of LV). G-CSF treated animals showed a significant improvement of post MI survival (68.8% vs. 46.2%). Pressure volume relations revealed a partially restored myocardial function at day 30 (EF: 32.5% vs. 17.2%). Our results demonstrate that G-CSF administration after MI stimulates arteriogenesis and attenuates ischemic cardiomyopathy after MI.