There is a large body of evidence that the liver microcirculation has to be considered as a major target in hepatic ischemia/reperfusion injury. The nature of microvascular injury, which precedes manifestation of hepatic parenchymal tissue damage, includes both hypoxia due to lack of microvascular perfusion (i.e. no-reflow), and a reperfusion-associated inflammatory response, which includes the activation and dysfunction of leukocytes and Kupffer cells (the reflow paradox). No-reflow in sinusoids is thought to be caused by endothelial cell swelling and intravascular hemoconcentration, and involves also a deterioration of the balance between ET and NO. The reflow paradox is associated with: (i) the release and action of proinflammatory cytokines (TNF-alpha, IL-1) and oxygen radicals; (ii) the up-regulation of endothelial and leukocytic adhesion molecules (selectins, beta-integrins, ICAM-1); and (iii) the interaction of leukocytes with the endothelial lining of the hepatic microvasculature.