Abstract: Renal ischemia-reperfusion injury (IRI) is an inevitable process in kidney transplantation and certain urological surgeries. IRI causes the release of injury-related molecular patterns by renal tubular epithelial cells, activating innate immune responses and sterile inflammation, leading to the persistence of immune infiltration and tissue remodeling processes, and promoting the transformation of acute kidney injury (AKI) to chronic kidney disease (CKD). CKD is mainly characterized by renal fibrosis, and is associated with the continuous infiltration of immune cells, the release of pro-inflammatory factors and the activation of pro-fibrotic signals. Estrogen receptor (ER) α can regulate the infiltration and activation of immune cells in multiple ways and inhibit renal fibrosis and CKD. This article reviews the specific molecular mechanisms by which ERα regulates immune cell infiltration and inhibits chronic fibrosis after renal IRI, with the aim of providing potential therapeutic targets and scientific basis for future AKI patients.