Motivation: Renal ischemia-reperfusion injury is one of the main causes of acute kidney injury. Medullary hypoxia occurs during reperfusion after ischemia, however, little is known of the mechanisms involved. The descending vasa recta mediate blood flow to the loop of Henle. These are capillary-sized microvessels, with contractile abluminal pericytes which could play a role in post-ischemic medullary hypoxia. We investigated if pericyte-mediated constriction of medullary descending vasa recta contributes to renal ischaemia. Methods: Adult male Sprague-Dawley rats (200-250 g; n=6-8) were anaesthetized with pentobarbital sodium. Both kidneys were exposed, and the renal arteries and veins were carefully dissected. Left kidneys were subjected to 60 min ischaemia induced by a renal artery and vein cross clamp followed by 30 min reperfusion (ISCH). The right kidneys underwent the same procedures but the blood perfusion was not blocked (SHAM). Two laser-doppler probes were used to measure simultaneously the renal perfusion in vivo on both kidneys. At the end of the ischaemia/reperfusion protocol animals were overdosed with pentobarbital sodium and transcardially perfused with saline followed by 4% for fixation and then 20 ml of 5% gelatin solution containing FITC-albumin to visualize the perfused renal microvasculature. Pericytes were labelled with anti-NG2 and anti-α-SMA antibodies and the capillary basement membrane and pericytes were labelled with isolectin B4-Alexa Fluor. Data are mean ± s.e.m and were analyzed using a unpaired Student’s t-test. Results: Ischaemia decreased renal perfusion by ~86% (p<0.0001), and this recovered 30 min following reperfusion. Perfusion was stable in the contralateral kidney (SHAM) throughout the experiment. Renal perfusion assessed ex vivo, as the mean intensity of FITC-albumin, demonstrated that renal ischaemia and reperfusion led to no-reflow in the medulla compared with the non-ischaemic kidneys (blood volume was reduced by ~50%, p< 0.0001). Similar reductions were seen in the medulla for the total microvessel length (p=0.038), the number of microvessel branches (p=0.053) and the overall microvascular density (p=0.0003). Ischaemia-induced medullary no-reflow was associated with blockages of the descending vasa recta. In ischaemic kidneys, the percentage of descending vasa recta blocked in the medulla of ischaemic kidneys was 78±9% compared with 10±4% in SHAM (p< 0.0001)., The descending vasa recta diameter at pericyte somata after ischaemia was reduced (4.4±0.4 µm; p=0.0001) compared with sham-operated kidneys (7.6±0.2 µm). The distance from blockage sites to the nearest pericyte soma was 4.9±0.4 µm (p< 0.0001), about 1/4 of the distance between pericytes, consistent with pericyte constriction generating the blockages. Conclusion: Medullary no-reflow reflects blockage by pericyte constriction of the descending vasa recta. Pericytes might be a therapeutic target for preventing renal medullary injury after ischaemia.