Activation of the Rho pathway mediates endothelial permeability and inflammation. Rho cycles between GTP-bound active and GDP-bound inactive states are regulated by GDI, GAP, and GEFs. Once activated, Rho induces MLC phosphorylation, resulting in an increase in actomyosin contractility and formation of actin stress fibers, leading to endothelial permeability. Simultaneously, activation of Rho also enhances ICAM-1 expression and facilitates neutrophil transmigration. GAP, GTPase activating protein; GDI, GDP dissociation inhibitor; GEF, guanine nucleotide exchange factor; ICAM-1, intercellular adhesion molecule-1; MLC, myosin light chain; Rho, Ras-homologous.