Endothelial cells play a key role in initiating and propagating the inflammatory response seen in ischemia, infections and sepsis. Situated in a key position between the epithelial cells and white blood cells (WBC), they interact and respond to signals from both cell types. Microvascular endothelial cells within the kidney mediate coagulation, WBC attachment, WBC migration into the interstitium, microvascular flow rates and permeability. Low regeneration potential and endothelial-mesenchymal transformation lead to fibrosis and subsequent microvascular dropout. This last event is in large part responsible for a chronic reduction in regional perfusion, subsequent increased vulnerability to recurrent acute kidney injury, and acceleration of chronic kidney disease progression to end-stage renal disease. Glomerular endothelial dysfunction may lead to preglomerular shunting of blood flow allowing kidney blood flow to remain close to normal while resulting in a reduction in glomerular filtration rate.