Most detailed measurements of microvascular function in animal models of the microcirculation involve direct observation on exposed microvascular beds to measure functional parameters describing network geometry, local blood flow, permeability in individual microvessels, and the interaction of inflammatory cells with the microvessel walls. Although these invasive approaches continue to be used for the physiological phenotyping of genetically modified animals, they are often limited to specific tissue (which may not express the phenotype) and are especially difficult to apply when the same animal must be repeatedly studied as the phenotype develops. Based on lessons learned from the more invasive approaches, we have begun to evaluate the use of magnetic resonance imaging (MRI), long- wavelength optical tracers, and microPET to measure independent changes in microvascular blood volume, increased vascular permeability, and localized accumulation of inflammatory cells in a range of tissues in mice over periods of hours, days or weeks. Projects begun in collaboration with laboratories at Bergen and Davis include the use of MRI to measure blood to tissue clearances normalized for changes in local vascular volume using a gadolinium based contrast agent with an apparent MW of 35 kDa, and the use of quantitative fluorescent imaging of albumin labeled with the long wavelength (Alexa) dyes to distinguish endothelial, neutrophil and platelet dependent mechanisms that regulate wound healing over periods of days.