Abstract： Objective： To investigate the mechanism of Shenshuai No.1 Formula administered by enema in the treatment of chronic kidney disease （CKD） based on network pharmacology， molecular docking， and animal experiments. Methods：Active components were screened from TCMSP，HERB，BATMAN，and TCMID databases.Disease targets of CKD were obtained from GeneCards，OMIM，DisGeNET，and CTD databases. Common targets were identified by intersection analysis. A component-target network and a protein-protein interaction （PPI） network were constructed， followed by Gene Ontology （GO） functional enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Molecular docking was performed using AutoDock Vina to verify the binding between key components and core targets. In vivo， CKD mouse models were established by intragastric administration of adenine at 40 mg/kg per day. Mice were divided into the normal control group （CTL），the CKD model group （CKD）， and the Shenshuai No.1 Formula administered by enema group （SSY）. Renal function was detected using an automatic biochemical analyzer； renal pathological changes were evaluated by histopathological staining； Western blotting was applied to detect the expression levels of typeⅠcollagen （CollagenⅠ），typeⅢcollagen （Collagen Ⅲ）， transforming growth factor-β1 （TGF-β1）， vimentin， and key proteins involved in the phosphatidylinositol 3-kinase/protein kinase B（ PI3K/AKT） signaling pathway in renal tissues. Results：A total of 212 potential therapeutic targets of Shenshuai No. 1 Formula against CKD were identified. Quercetin，luteolin，and wogonin were identified as major active components. Core targets screened out by PPI network analysis were tumor protein p53 （TP53）， signal transducer and activator of transcription 3 （STAT3） ， AKT1， SRC proto-oncogene non-receptor tyrosine kinase （SRC）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha （PIK3CA）. KEGG enrichment indicated that the PI3K/AKT signaling pathway was a potential key pathway. Molecular docking confirmed that quercetin， luteolin， and wogonin could stably bind to the active pockets of AKT1 and PIK3CA. Animal experiments demonstrated that Shenshuai No.1 Formula significantly reduced serum creatinine （SCr） and blood urea nitrogen （BUN） levels in CKD mice，and downregulated the expression of CollagenⅠ，CollagenⅢ，TGF-β1，and vimentin in renal tissues. Further mechanistic studies revealed that Shenshuai No. 1 Formula inhibited the phosphorylation of PI3K and AKT， and decreased the p-PI3K/PI3K and p-AKT/AKT ratios in renal tissues of CKD mice. Conclusion：Shenshuai No. 1 Formula may alleviate renal fibrosis by suppressing the overactivation of the PI3K/ AKT pathway，thereby exerting a renal protective effect in the treatment of CKD.