The article reviews the pathophysiology of ischemia-reperfusion (I/R) injury, focusing on microvascular dysfunction. I/R injury is characterized by impaired endothelium-dependent dilation in arterioles, enhanced fluid filtration and leukocyte plugging in capillaries, and leukocyte and plasma protein extravasation in postcapillary venules. Activated endothelial cells produce more oxygen radicals but less nitric oxide, leading to an imbalance that promotes the production of inflammatory mediators and the biosynthesis of adhesion molecules. Risk factors such as hypercholesterolemia, hypertension, and diabetes exacerbate microvascular alterations elicited by I/R. The inflammatory mediators released during reperfusion can also activate endothelial cells in remote organs, leading to leukocyte-dependent microvascular injury and multiple organ dysfunction syndrome (MODS). The article discusses the mechanisms underlying these responses and highlights the phenomenon of ischemic preconditioning, which protects tissues from the harmful effects of subsequent prolonged ischemia. Two types of preconditioning are distinguished: acute and delayed, with distinct mechanisms and requirements for protein synthesis. The review also explores the role of xanthine oxidase, leukocytes, and inflammatory mediators in remote organ injury and the adaptive responses that mitigate I/R injury.The article reviews the pathophysiology of ischemia-reperfusion (I/R) injury, focusing on microvascular dysfunction. I/R injury is characterized by impaired endothelium-dependent dilation in arterioles, enhanced fluid filtration and leukocyte plugging in capillaries, and leukocyte and plasma protein extravasation in postcapillary venules. Activated endothelial cells produce more oxygen radicals but less nitric oxide, leading to an imbalance that promotes the production of inflammatory mediators and the biosynthesis of adhesion molecules. Risk factors such as hypercholesterolemia, hypertension, and diabetes exacerbate microvascular alterations elicited by I/R. The inflammatory mediators released during reperfusion can also activate endothelial cells in remote organs, leading to leukocyte-dependent microvascular injury and multiple organ dysfunction syndrome (MODS). The article discusses the mechanisms underlying these responses and highlights the phenomenon of ischemic preconditioning, which protects tissues from the harmful effects of subsequent prolonged ischemia. Two types of preconditioning are distinguished: acute and delayed, with distinct mechanisms and requirements for protein synthesis. The review also explores the role of xanthine oxidase, leukocytes, and inflammatory mediators in remote organ injury and the adaptive responses that mitigate I/R injury.