Introduction: Kidney ischemic-reperfusion injury (IRI) is the main cause of acute kidney injury (AKI) which leads to the inflammation epithelial apoptosis and interstitial fibrosis as the chronic consequenses. Centella asiatica (CeA) has been known to have various pharmacological effects such as, anti-inflammatory, antioxidant, anti-fibrosis, and, anti-apoptosis. We aimed to elucidate the role of CeA in inhibiting kidney injury and infammatory mediators due to kidney IRI. Methods: Kidney IRI were performed with bilateral renal pedicles clamping in Swiss background mice (3 months-old, 30-40 grams) for 30 minutes (IR group, n=6), then terminated at day 7 after operation. At the next day, the mice that have been underwent bilateral kidney IRI were administered per-orally with ethanolic extract of CeA (210 mg/kg of BW, CeA1 group, n=6, and 420 mg/kg of BW, CeA2 group, n=6). The Sham Operation (SO group, n=6) was used as control. At the day 7 after the surgery, the mice were sacrificed and the kidneys were harvested. The kidney was used to assess tubular injury, interstitial fibrosis, and macrophage number, and another kidney was used to assess the mRNA expression of TLR4. Data were quantified using SPSS 22. Results: Kidney IRI produced significantly higher tubular injury, interstitial fibrosis and macrophage number (p<0.05) compared to SO with upregulating TLR4 mRNA expression (p<0.05). CeA treatment attenuated the tubular injury, interstitial fibrosis, macrophage number, and TLR4 mRNA expression which obviously shown in higher-dose of CeA (p<0.05). Conclusion: CeA ameliorates tubular injury, kidney fibrosis, and inflammatory mediators due to kidney IRI.