Background. The present work was designed to study the effects of methanolic stevia extracts and aerobic exercise and combination of both on renal I/R injury in male rats. Methods. 60 adult male Sprague-Dawley rats were subdivided into five equal groups as sham, control, exercise, stevia, and stevia plus exercise group. After 5 weeks of exercise and stevia, animals were exposed to 45 min of left renal ischemia and right nephrectomy followed by reperfusion. Serum creatinine, creatinine clearance, fractional Na excretion (FE Na +), malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT) levels in kidney tissues were measured. Also, renal histopathology and the expression of caspase-3 by immunohistochemical examination were done. Results. The results showed that stevia, exercise or combination of stevia and exercise caused a significant decrease in serum level of creatinine (p < 0.001) and FE Na + (p < 0.001) and an increase in creatinine clearance (p < 0.001). Moreover, this caused a significant decrease in (MDA; p < 0.046) and an increase in GSH (p < 0.01) and CAT (p < 0.01), as well as causing a significant decrease in caspase 3 expression compared to the control group. Conclusion. Pretreatment with either stevia or exercise of combination of both seem to have protective effects on renal I/R injury. However, the protective effect of exercise against renal I/R injury seems to be less than stevia. These effects might be due to attenuation of oxidative stress and apoptosis in kidney tissues.