Organ dysfunction followed by single-organ, or even multi-organ failure, due to ischaemia-reperfusion injury (I/RI) is a common complication in transplant, liver, trauma, and heart surgery (Clavien et al.). Here we report that FTY720, an analogue of sphingosine 1-phosphate, attenuates ischemia-reperfusion damage in the rat’s atrio-ventricular node (AVN) preparations. Isolated rat AVN was prepared according to established method (Lei, Jones et al. 2004) and fixed in a tissue-perfusion chamber. The Preparation was superfused with control oxygenated Tyrode solution at a rate of 4 ml/min at 37 0C through a heat exchanger, then exposed to ischemic-like condition (omission of glucose and adjusted pH to 6.6 based on Tyrode solution) for 15 mins, the preparation was finally re-perfused with control Tyrode solution. Extracellular potentials were recorded by two bipolar electrodes from the preparation. The cycle length (CL) of the AVN preparations without treatment of FTY720 was prolonged by 67 % and 17 % in ischemia (CL: 716 ± 21 ms, n= 7) and reperfusion (501 ± 21 ms, n=7) conditions from the control condition (CL: 429 ± 18 ms, n = 7). The CL of AVNs treated with 25 nM FTY720 for 15 mins was prolonged by 5% and 15% in ischemia condition (CL: 446 ± 71 ms, n= 8) and reperfusion conditions (494 ± 70 ms, n=8) from the control condition (CL: 428±10 ms, n=8), the prolongation of CL is therefore significantly less than these preparations without FTY720 treatment. Our results indicate that FTY720 significantly attenuates ischemia-reperfusion damage in the rat’s AVN preparations and it represents a new approach to treatment of the many clinical disorders in which ischemia-reperfusion occurs. The mechanism for FTY720 protective effect requires a further investigation.