Microvessel ensheathment is initiated by BDNF/TrkB signaling, which is regulated by RhoA pathway and is sensitive to RhoA kinase (ROCK) inhibition. During inflammation and tissue injury pericytes are able to detach from the microvessel wall and transdifferentiate into fibrillar extracellular matrix (ECM)-producing myofibroblasts. Deposition of ECM leads to fibrosis and organ failure. Fibrosis is regulated by JNK and TGFβ/Smad pathways, which cross-talk with RhoA pathway. Inhibition of JNK and TGFβ/Smad through the inhibition of RhoA kinase ROCK abrogates collagen production and fibrosis. Detachment of pericytes from the microvessel wall is regulated by the Ang/Tie pathway, which cross-talks with RhoA signaling. Because RhoA is a master regulator of actin-related cell functions it also regulates pericyte contractility. By crosstalking to Ang/ Tie-2 and SEMAD4D/Plexin-B1/ANGPTL4 pathways, RhoA signaling influences pericyte differentiation and pericyte coverage, which in turn regulate blood flow and overall vessel permeability.