Blood vessel growth, angiogenesis, is a tightly regulated process involving not only endothelial cells, but also several different cell types. Leukocytes are known to accumulate at sites of hypoxia and were recently identified as key players in the process of vessel neo-formation. Recognition of leukocyte involvement in angiogenesis has unlocked a new research area especially focusing on tumor vascularization, but the dynamics of leukocyte involvement in angiogenesis, as well as their exact pro-angiogenic actions are still largely unknown. To address this, we developed a model that allows for in vivo visualization and tracking of leukocytes at the site of angiogenesis. Isolated pancreatic islets are transplanted to the cremaster muscle of genetically identical recipient mice. Leukocytes, endothelial cells and blood flow at the site of islet transplantation are studied in parallel at different time points following transplantation using high-speed in vivo confocal microscopy. We found that isolated islets transplanted to striated muscle rapidly regained their dense, glomeruli-like capillary network. Neutrophils were crucial for initiation of this process and islets transplanted to neutropenic mice did not become revascularized. In fact, a distinct neutrophil subset with proangiogenic actions was recruited from the circulation to the site of hypoxia by islet-derived vascular endothelial growth factor A (VEGF-A), the main angiogenic factor. Proinflammatory neutrophils were not recruited by VEGF-A and expressed distinct lower levels of the chemokine receptor CXCR4 compared to the proangiogenic subset. Proangiogenic neutrophils delivered highly active MMP-9 (matrix metalloproteinase 9) known to be important for angiogenesis to the site of islet transplantation. The role of neutrophil-derived MMP-9 was demonstrated by transplanting islets to MMP-9 deficient mice, which resulted in severely delayed development of the intra-islet capillary network as well as an altered vascular network at later time points following transplantation. Further, our data imply the existence of two separate neutrophil lineages already in circulation based on the levels of CXCR4. These different neutrophil subsets did not change phenotype by in vitro stimulation with MIP-2 (CXCL2) or VEGF-A. Not only neutrophils exert proangiogenic actions, and ongoing studies in my laboratory address both neutrophil and monocyte recruitment to sites of hypoxia, as well as the different roles of neutrophils and macrophages for vessel neo-formation and maturation. We also track the migration pattern and cellular interactions of the different cell types to understand the respectively driving force and actions during angiogenesis. Thus, by using a new in vivo imaging model for studying the behavior and actions of different leukocyte populations during angiogenesis, important information of their identities and actions are gained. We found that neutrophils and macrophages have very different, but profound roles and effects on the revascularization of transplanted pancreatic islets.