To study the role of hemodynamic stresses in microvascular network remodeling, a ligation strategy was developed to locally alter pressure and wall strain throughout the microvessel network of a single mesentery window. Additionally, a network model was developed to calculate the pre- and post-ligation pressures throughout the affected mesenteric microvessel networks. The ligations caused a significant (P<0.05) 19% increase in diameter throughout the measured networks. There was no statistically significant change in the wall shear rate due to ligation. Based on a representative network whose dimensions were recorded before and after ligation, the network model predicted an average pressure increase of 4.4% throughout the theoretical network with the largest increases (8.3%) occurring in the small arteriolar vessels. When the ligations were maintained for one week or seven days, a 5-fold increase in vessel length density was observed throughout the affected mesentery window.