Introduction: Renal ischemia-reperfusion injury (IRI) is frequently encountered in trauma, transplant and vascular surgery. Adenosine (ADE) is a vasoactive nucleoside shown to attenuate myocardial and skeletal muscle IRI. We evaluated the ability of adenosine, when given after renal ischemia, to reduce renal ischemia-reperftision injury. Methods: Sixteen New Zealand white rabbits were divided into two groups. All rabbits underwent a laparotomy, with bilateral renal artery cross-clamping for 45 minutes, followed by 72 hours of reperfusion. Group 1 (control, N=10) animals received a 0.9% normal saline infusion for the first 4.5 hours of reperfusion. In addition to saline, Group 2 (ADE, N=6) animals received, at 30 minutes after removal of the renal artery clamps, an infusion of ADE 350 μg/kg/min IV for 10 minutes. Baseline and 72-hour serum creatinine (Cr), and blood urea nitrogen (BUN) levels were measured, and the rabbits were sacrificed after 72 hours of reperfusion. Mann-Whitney rank sum statistical analysis was utilized with α set at p < 0.05. Results: There was no significant difference in baseline BUN or Cr between the two groups. Group 1 animals had a significantly greater increase in both Cr (p < 0.006) and BUN (p < 0.003) compared to Group 2, indicating that renal function was preserved in the animals receiving the adenosine infusion. Group 1 Control N = 10 Group 2 ADE N = 6 P Value Cr change (Mean ± 1 SD) 1.56 ± 2.19 -0.07 ± 0.20 < 0.006 BUN change (Mean ± 1 SD) 34.9 ± 37.5 1.33 ± 2.73 < 0.003 Conclusions: Administration of adenosine 30 minutes into reperfusion attenuates renal ischemia-reperfusion injury in this rabbit model. Further studies are necessary to evaluate the feasibility of using adenosine therapeutically in renal ischemia-reperfusion injury.