Objective To evaluate the protective effect of epigallocatechin gallate (EGCG) on acute kidney injury induced by cisplatin (CIS) in rats based on network pharmacology. Methods 32 male Wistar rats were randomly divided into four groups as follows: control group (CON group),EGCG group, CIS group (cisplatin group) and CIS+EGCG group. CON group and CIS group were given normal saline every day, EGCG and CIS+EGCG group were given EGCG (40 mg/kg) every day for 28 days. On the 26th day, CIS group and CIS+EGCG group were intraperitoneally injected with cisplatin (7 mg/kg).On the 29th day, blood and tissue were taken from each group. The levels of serum urea nitrogen (BUN) and creatinine (SCr) were detected, renal pathological changes were observed by HE staining, TUNEL was used to detect apoptosis in renal tissue. Drugs and disease targets were screened by TCMSP, Gene Cards and OMIM websites, protein-protein interaction network (PPI) was constructed after intersection, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) enrichment analysis were carried out, and the results were verified by Western Blot 、RT-QPCR and immunohistochemistry. Results The results showed that EGCG preconditioning significantly decreased the levels of BUN and SCr in serum of AKI rats and improved the nephropathy of AKI rats, and relieved the renal tissue apoptosis of AKI rats. 87 EGCG and AKI intersection genes and 25 core targets were screened by network pharmacology, which affected the development of AKI through PI3K/AKT and other signal pathways and a variety of biological processes. Conclusions EGCG alleviates CIS-induced acute kidney injury in rats through PI3K-AKT signaling pathway.