The CAM is a thin, respiratory Moexipril HCl tissue for the developing chick embryo characterized by a dense, highly organized network of blood vessels. The physiological Octinoxate responses of the CAM are consistent with those of mammalian tissues and it has provided a physiologically relevant setting for angiogenesis research for more than a century. The commercial availability of fertilized eggs, the ease of embryo culture, and the robustness of the CAM model facilitate large, statistically powerful studies and make it suitable for high throughput approaches. The CAM is not fully immunocompetent in the early embryo, and it supports the growth of human and murine tumor xenografts. In addition, in the exovo model, the CAM is directly accessible for experimental manipulation and imaging. Paired with a fluorescence microscopy platform, this model is well-suited for analyzing drug-induced changes in vascular permeability in tumor xenografts and their microenvironment. We demonstrate, using this intravital imaging approach, that vascular permeability can be manipulated to modulate the extravasation of small molecules into the local tumor microenvironment. Treatment with vascular endothelial growth factor or a permeability enhancing peptide fragment of IL-2 either locally or systemically results in a temporary enhancement of vascular permeability that can be precisely monitored over time. We show that this transient increase in vascular permeability can be exploited to significantly enhance the accumulation of a chemotherapeutic drug within the tumor. Here, we present a novel approach to visualize and quantitate hemodynamics and vascular leak in tumors. In contrast to traditional, endpoint analysis methods, real-time intravital imaging is sensitive to changes in both permeability and vessel integrity, and can effectively track rapid and dynamic changes in vascular permeability. We demonstrate that vascular permeability is increased in xenograft tumors compared to distal normal tissues, and that it can be further enhanced by VEGF and the PEP fragment of IL-2.