One of the key signaling molecules that play a major role in inflammation is ROS. Polymorphonuclear neutrophils enhance and activate the generation of ROS at the site of the endothelial dysfunction and tissue injury. The migration of inflammatory cells from blood to tissue is facilitated by the vascular endothelium. Followed by the inflammation there is opening of indo-endothelial junction through which migration of inflammatory cells takes place. The migration of inflammatory cells across the endothelial barrier not only clears the way to pathogens and foreign particles but also causes serious tissue injury. This review highlights the oxidative stress mediated signaling mechanisms involved in inflammation leading to serious illnesses like diabetes.