Background: Acute kidney injury (AKI) is a kidney disease resulting in high morbidity and mortality levels in humans. One of the disorders classified as AKI is ischemia-reperfusion injury (IRI), characterized by two phases. The first phase is Ischemia in the kidneys due to obstruction of the renal arteries or veins, followed by the second phase, which is the occurrence of reperfusion with blood flowing back in the renal arteries veins. The aim of this current research is to analyze the efficacy of Artocarpus altilis on Kidney ischemia-reperfusion model rats. Methods: To this end, first, we established Ischaemia-reperfusion kidney injury rat. We then evaluated the Artocarpus altilis extract on IRI model rats. A total of 36 rats have grouped into six groups. Group I is the Sham group, Group II is the negative control group, Group III is the positive control group (vitamin C 100 mg/kg BW), Group IV is Dose I of Artocarpus altilis extract 50 mg/kg BW), Group V is Dose II Artocarpus altilis extract 100 mg/kg BW), Group VI is Dose III Artocarpus altilis extract 200 mg/kg BW). The vitamin C and Artocarpus altilis extract administered 14 days before and after Ischemia-reperfusion treatment. At day 0, Ischemia was made by bilateral renal pedicle clamping method for 30 minutes, sacrificed 14 days after reperfusion. The blood and histology samples were collected on day 0, a day after reperfusion, at 24 hrs after reperfusion, at 48 hrs after reperfusion, and 14 days after treatment. Results: The clamping duration of 30 minutes leads to achieving the most representative clinical IRI conditions. It shows the most significant recovery of injury conditions within the 14-day reperfusion period in IRI animal models, making it ideal for IRI operations for the preliminary test. The administration of 100 mg/kg BW of Artocarpus altilis extract could reduce the malondialdehyde plasma compared with the sham group. The SOD and Catalase activity showed improvement after reperfusion. Conclusion: Artocarpus altilis extracts showed antioxidant activity to prevent the kidney from ischemia-reperfusion injury by modulated SOD and Catalase. © 2021 Phcogj.Com. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.