Reactive oxygen species (ROS) play a crucial role in the progression of inflammatory disorders by causing endothelial dysfunction and tissue injury. The vascular endothelium, which facilitates the passage of macromolecules and inflammatory cells from the blood to tissues, is particularly affected. Oxidative stress produced by polymorphonuclear neutrophils (PMNs) leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. This migration of inflammatory cells helps clear pathogens and foreign particles but also contributes to tissue damage. The current review compiles past and current research on inflammation, focusing on oxidative stress-mediated signaling mechanisms involved in inflammation and tissue injury. It covers the sources of ROS, their regulation, and the structural basis of endothelial integrity, as well as the signaling mechanisms of endothelial barrier disruption by oxidative stress. The review highlights the importance of ROS in inflammation and the role of antioxidant defense systems in mitigating their damaging effects.Reactive oxygen species (ROS) play a crucial role in the progression of inflammatory disorders by causing endothelial dysfunction and tissue injury. The vascular endothelium, which facilitates the passage of macromolecules and inflammatory cells from the blood to tissues, is particularly affected. Oxidative stress produced by polymorphonuclear neutrophils (PMNs) leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. This migration of inflammatory cells helps clear pathogens and foreign particles but also contributes to tissue damage. The current review compiles past and current research on inflammation, focusing on oxidative stress-mediated signaling mechanisms involved in inflammation and tissue injury. It covers the sources of ROS, their regulation, and the structural basis of endothelial integrity, as well as the signaling mechanisms of endothelial barrier disruption by oxidative stress. The review highlights the importance of ROS in inflammation and the role of antioxidant defense systems in mitigating their damaging effects.