Background: Reperfusion or reoxygenation of cardiac tissue after an ischemic period is a challenging situation for cardiac tissue, because immediate restoration of energy supply by the electron transport chain of the mitochondria is mandatory for functional recovery but also risky as it may add oxidative stress. Recovery of mitochondria function and controlling electron transport velocity is therefore a strictly controlled mechanism allowing the mitochondria to supply the cell with energy and control oxidative stress evoked by mitochondria. For this control the uncoupling properties of uncoupling protein 2 (UCP2), the main UCP isoform expressed in the heart, seems of specific relevance. Hearts from mice and rats differ in the cellular distribution of UCP2 as UCP2 expression in mice hearts is predominantly seen in non-myocytes but the expression of UCP2 is rather high in rat myocytes. Therefore, one would expect species differences between mice and rats if UCP2 plays an important role in this process. In the current study we used ex vivo perfused hearts from wild-type and UCP2 deficient mice and rats to clarify the role of UCP2 for reperfusion injury. Results: We compared the functional recovery of ten male WT mice and eight male UCP2 ko mice. No-flow perfusion was used as an index ischemia of 45 min and subsequently the hearts were reperfused for two hours. WT and KO mice did not differ in left ventricular developed pressure (LVDP), dp/dt max, and dp/dt min prior to ischemia. During ischemia rigor contraction increased the pressure in WT mice (52.2 mmHg) and KO mice (51.3 mmHg) similarly. Two hours after reperfusion, LVDP was recovered to 59.5 % und 61.7%, in WT and KO mice respectively. 90% of WT mice and 100% of KO mice had difficulties to perform regular beating during the first 15 min of reperfusion but regular beating was observed thereafter. Similarly to the mouse model, no significant difference occurred in male WT (n=22) and KO (n=15) rats prior to ischemia. Again, ischemia increased rigor contraction to 48.4 and 42.7 mmHg, in WT and KO rats, respectively. Functional recovery (LVDP) was 65.0 % in WT rats and 68.1 % in KO rats. 10% of WT rats and 40% of KO rats had difficulties to perform regular beating during the first 15 min of reperfusion.  Interestingly, a subgroup analysis revealed detrimental effects of UCP2 deficiency in rats with strong ischemic damage (rigor contraction above 50 mmHg; 58.1 and 57.3 mmHg in WT and KO, respectively).  In these rats (WT: 10 rats; KO: 7 rats) LVDP recovery was 57.3 % in WT rats but only 46.0 % in KO rats. 10% of these WT rats and 60% of these KO rats had difficulties to perform regular beating during the first 15 min of reperfusion. ROS detection assay by amplex ultra red fluorescence in isolated mitochondria from rat hearts revealed no differences between WT and UCP2 KO rats. Conclusion: The data of our study show that mild uncoupling of mitochondria has a minor effect on functional recovery after an ischemia period. The conclusion is based on our similar finding in mice and rats with different cellular distribution of UCP2 expression. However, uncoupling by UCP2 may contribute to protection against arrhythmia and functional recovery after severe infarcts. However, the mechanism by which UCP2 exerts this effect is independent of oxidative stress.