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Abstract ObjectiveFluid shear stress is thought to be a regulator of endothelial cell behavior during angiogenesis. The link, however, requires an understanding of stress values at the capillary level in angiogenic microvascular networks. Critical questions remain. What are the stresses? Do capillaries experience similar stress magnitudes? Can variations explain vessel‐specific behavior? The objective of this study was to estimate segment‐specific shear stresses in angiogenic networks. MethodsImages of angiogenic networks characterized by increased vascular density were obtained from rat mesenteric tissues stimulated by compound 48/80‐induced mast cell degranulation. Vessels were identified by perfusion of a 40 kDa fixable dextran prior to harvesting and immunolabeling for PECAM. Using a network flow‐based segment model with physiologically relevant parameters, stresses were computed per vessel for regions across multiple networks. ResultsStresses ranged from 0.003 to 2328.1 dyne/cm²and varied dramatically at the capillary level. For all regions, the maximum segmental shear stresses were for capillary segments. Stresses along proximal capillaries branching from arteriole inlets were increased compared to stresses along capillaries in more distal regions. ConclusionsThe results highlight the variability of shear stresses along angiogenic capillaries and motivate new discussions on how endothelial cells may respond in vivo to segment‐specific microenvironment during angiogenesis.