Initial pathological events in the kidney following renal ischemia-reperfusion (I-R)-ischemia injury include vasoconstriction, endothelial cell activation, tubular swelling, epithelial necrosis and interstitial edema. Organ reperfusion increases endothelial expression of adhesion molecules, promotes leukocyte recruitment and activation giving way to increased reactive oxygen species production and the development of the inflammatory process that is a major contributor to the injury observed after I-R. Nitric oxide (NO) appears to bea key link between I-R injury and the rate of tissue repair. NO is also involved in inflammation, tissue injury, and cell defense. Although it has been shown that NO production is increased in the kidney after I-R, it seems that this increase derives from iNOS overexpression, and most of its effects contribute to the renal injury, whereas there is a marked alteration in endothelial function, associated to a decrease in endothelial NO synthase (eNOS) activity. Activity of eNOS predominates in the beneficial effects of NO in recovery from I-R injury. Among the beneficial effects of eNOS-derived NO on I-R injury it has been shown that NO inhibits platelet adhesion and aggregation thus avoiding vascular thrombosis during reperfusion, NO is able to block monocyte adherence and migration, NO is an inhibitor of leukocyte activation, may also prevent the liberation of products with cytotoxic and vasoconstrictor properties (leukotrienes, cytokines, prostaglandins), and may have a direct cytoprotective effect on the endothelial cell during the inflammatory reaction. Administration of exogenous NO donors can substitute the effect of deficient eNOS-derived NO on I-R injury.