Heart failure following infection is one of the most important causes of death throughout the world. This study was undertaken to investigate the protective effects of metformin on apoptotic cell death of renal during experimental renal ischemia/reperfusion in (I/R) rats. Twenty-five male Wistar rats were randomly assigned into 5 groups of 5 animals each, including: 1. sham, 2. I/R, 3. low-dose metformin + I/R, 4. average dose metformin + I/R and 5. high-dose metformin + I/R. Renal ischemia was induced clamping the renal artery. After 30 min of ischemia, the clamps were taken off and the animals underwent 2 h reperfusion. Metformin (5, 10, and 20 µg/kg/min) was infused 15 min prior to reperfusion through the jugular vein in treatment groups. At the end of the experiment, the rats were euthanized and histological sections from renal tissue were prepared through the TUNEL method. Apoptotic cells were counted under light microscope. The data obtained were statistically analyzed using ANOVA. Differences were considered statistically significant at p ≤ 0.05. In group 2, ischemia/reperfusion caused occurrence of apoptotic cell death in renal tissue. There was a significant increase in the incidence rate of apoptosis of renal in comparison with group 1 (p ≤ 0.001). In groups 3–5, metformin (5, 10 and 20 µg/kg/min) caused significant decrease in the number of apoptotic cells in comparison with group 2 (p ≤ 0.05, p ≤ 0.01 and p ≤ 0.001, respectively). This study, therefore, suggests that metformin may be a useful agent for the prevention of ischemia/reperfusion-induced apoptotic cell death of renal in a dose-dependent manner in rats.