Objective: C57Bl/6 mice were divided into the following groups: sham; Rg3 treated sham; saline treated IRImice; Rg3 treated IRI mice. Kidneys and blood were collected 24h after operation of mice (sham and IRoperation). Renal function, kidney histology, and the protein expression of autophagy signals were evaluated. Methods: In IRI mice, the levels of BUN and s-Cr were increased, compared to sham. The Rg3 treatmentdecreased the BUN and s-Cr in IRI mice. In addition, Rg3 treatment decreased the renal injury score includingthe renal tubular cell detachment and necrosis in IRI mice. Rg3 treated IRI mice showed significantly lessoxidative stress and autophagy impairment, greater amounts of LC3 and Beclin-1, lower amounts of p62, andhigher levels of renal ATP6E compared to saline treated IRI mice. Rg3 treatment also increasedphosphorylation of AMPK in IRI mice kidney. Results: Rg3 has renoprotection against renal IR injury via enhancement of autophagy flux. Conclusions: Objective: Ginsenoside Rg3 (Rg3) has been shown as protective effects via various mechanism. However,the reno-protective effect and the role of autophagy are not clearly evaluated. This study investigate Rg3induces autophagy flux and reduces renal cell death in renal ischemia reperfusion injury (IRI). Methods: C57Bl/6 mice were divided into the following groups: sham; Rg3 treated sham; saline treated IRImice; Rg3 treated IRI mice. Kidneys and blood were collected 24h after operation of mice (sham and IRoperation). Renal function, kidney histology, and the protein expression of autophagy signals were evaluated. Results: In IRI mice, the levels of BUN and s-Cr were increased, compared to sham. The Rg3 treatmentdecreased the BUN and s-Cr in IRI mice. In addition, Rg3 treatment decreased the renal injury score includingthe renal tubular cell detachment and necrosis in IRI mice. Rg3 treated IRI mice showed significantly lessoxidative stress and autophagy impairment, greater amounts of LC3 and Beclin-1, lower amounts of p62, andhigher levels of renal ATP6E compared to saline treated IRI mice. Rg3 treatment also increasedphosphorylation of AMPK in IRI mice kidney. Conclusions: Rg3 has renoprotection against renal IR injury via enhancement of autophagy flux.