Although preclinical and clinical studies have demonstrated that relaxin (RLX) ameliorates impaired renal function by exerting antifibrotic and regenerative effects, its role in renal ischemia/reperfusion (I/R) injury has never been investigated. Using a well-known rat model of 1 h bilateral renal artery occlusion followed by 6 h reperfusion, we investigated the effects of human recombinant RLX (5 microg /Kg e.v.) given both at the beginning and after 3 h reperfusion. Serum and urinary indicators of renal injury and dysfunction were measured. Interestingly, administration of the exogenous RLX attenuated all markers of renal injury and dysfunction caused by I/R. Overall, we document here, for the first time, that RLX protects against I/R-induced renal injury and dysfunction. The results of this study offer good perspectives for the clinical potential of RLX in the medical treatment of renal diseases.