Annexin A2 has been shown to act as a receptor for plasminogen (Plg) and its tissue type activator (tPA) in endothelial cells (EC). Aim of the present study was to elucidate the renal distribution of the components of this complex under control conditions and in a Thy1 nephritis model of proteinuric renal disease. Thy1 nephritis was induced by intravenous injection of OX7 anti‐Thy1 antibody (1mg/kg body weight). Distribution of Plg, tPA and ANXA2 was studied by immunofluorescence in controls and after 5 or 15 days of OX7 injection. Immunoreactive structures were further characterized by double‐labeling immunofluorescence using antibodies against rat endothelial cell antigen for EC, Na(+),K(+),2Cl(−) cotransporter for thick ascending limbs (TAL), aquaporin‐1 for thin descending limbs (tDL) and aquaporin‐2 for collecting ducts (CD). As expected, all three proteins were identified in EC of controls and Thy1 animals. In addition we found overlapping signal for tPA, Plg and ANXA2 in the basolateral and apical membrane of tDL, TAL and CD both, in treated and untreated animals. Furthermore, abundance of tPA and Plg in the apical membrane of TAL and CD was increased in proteinuric animals. In conclusion, our results provide evidence for the presence of a proteolytic complex in the apical membrane of renal epithelia where it may play a protective role in the setting of proteinuric disease.support: DFG FOR 667