During renal ischemia/reperfusion (I/R) injury, apoptosis has been reported as a very important contributor to the final kidney damage. The determinant role of cytoskeleton derangement in the development of apoptosis has been previously reported, but a clear description of the different mechanismes involved in this process has not been yet provided. The aim of our study is to know the role of peroxynitrite as inductor of cytoskeleton derangement and apoptosis during renal ischemia-reperfusion. Based in a rat kidney I/R model, by experiments in which both the actin cytoskeleton and peroxynitrite generation were pharmacologically manipulated, results indicate that the peroxynitrite produced during the I/R derived oxidative stress state, is able to provoke cytoskeleton derangement and apoptosis development. Thus, the control in the peroxynitrite generation during the I/R could be an effective tool for the improvement of cytoskeleton damage and reduction apoptosis incidence in the renal I/R injury.