The use of intravital fluorescence microscopy in the models of the hamster dorsal skin fold chamber and the ear of the hairless mouse allows for the quantitative analysis of post-ischemic microvascular reperfusion injury in striated muscle and skin. Prolonged periods of ischemia (4 hours in striated muscle and 6 hours in skin) are associated with 1) perfusion failure of nutritive capillaries at the onset of reperfusion (no-reflow) and 2) activation, accumulation and microvascular adherence of white blood cells, formation of reactive oxygen metabolites and release of potent mediators (leukotrienes, platelet-activating factor) with the consequence of increased microvascular permeability due to the loss of endothelial integrity, interstitial edema and cell damage (reflow-paradox). Prophylactic and/or therapeutic regimens may, therefore, include improvement of capillary perfusion by hemodilution, and inhibition of leukocyte adherence, radical formation and mediator release by appropriate counteracting compounds, including anti-oxidants, antibodies directed against adhesion molecules, leukotriene synthesis inhibitors and platelet-activating factor receptor antagonists.