Renal ischemia/reperfusion (I/R) injury is the main cause of acute renal failure. The severity of injury is determined by endothelial damage as well as inflammatory and apoptotic processes. The anti-coagulants active site inhibited factor VIIa (ASIS) and activated protein C (APC) are besides their anti-coagulant function also known for their cytoprotective properties. In this study the effect of ASIS and APC was assessed on renal I/R injury and this in relation to inflammation and apoptosis. Our results showed no effect of ASIS or APC on renal injury as determined by histopathological scoring as well as by BUN and creatinin levels. Furthermore, no effect on fibrin staining was detected but ASIS did reduce TF activity levels after a 2 hrs reperfusion period. Neither ASIS nor APC administration influenced overall inflammation markers, although some inflammatory effects of ASIS on interleukin (IL)-1β and tumor necrosis factor (TNF)-α were detectable after 2 hrs of reperfusion. Finally, neither APC nor ASIS had an influence on cell signaling pathways or on the number of apoptotic cells within the kidneys. From this study we can conclude that the anti-coagulants ASIS and APC do not have protective effects in renal I/R injury in the experimental setup as used in this study which is in contrast to the protective effects of these anti-coagulants in other models of I/R.