Background: Microvascular dysfunction develops in tissues after Ischemia-Reperfusion (IR). The current study aimed to determine the effect of naringin supplementation on kidney caspase-3, IL-1β, and HIF-1α levels and kidney histology in rats undergoing unilateral nephrectomy and kidney-ischemia reperfusion. Methods: The study was conducted on 8-12 weeks old 40 Wistar-type male rats. Experimental renal ischemia-reperfusion and unilateral nephrectomy were performed under general anesthesia in rats. Experimental groups were formed as follows: 1-Control group, 2-Sham control + Vehicle group, 3- Renal ischemia-reperfusion (Renal I+R) + Vehicle group, 4-Renal I+R + Naringin (50 mg/kg/day) group (3 days application) group, 5-Renal I+R + Naringin (100 mg/kg/day) group (3 days supplementation). Nephrectomy in the left kidneys and the ischemia for 45 minutes and reperfusion in the right kidneys followed by 72 hours of reperfusion. Naringin was administered intraperitoneally at the beginning of the reperfusion, 24 hours and 48 hours later. At the end of the experiments, blood was first taken from the heart in animals under general anesthesia. Then, the animals were killed by cervical dislocation, and kidney tissue samples were taken. Tissues were evaluated for caspase-3, IL-1β, and HIF-1α as well as histologically. Results: As a result of ischemia in kidney tissues, HIF-1α decreased, while caspase-3 and IL-1β increased. IR also caused damage to the kidney tissue. However, naringin supplementation corrected the deterioration to a certain extent. Conclusion: The results of the study showed that naringin may have protective effects on kidney damage due to anti-inflammatory and antiapoptosis mechanisms caused by unilateral nephrectomy and IR in rats.