This proteomics analysis in this study examined renal tissue protein expression profiles in adenine-induced chronic kidney disease (CKD) rats, focusing on the differences between the CKD group and the group treated with a high dose of Jianpi Yishen (JPYS) formula. It revealed that JPYS induces significant proteome reprogramming, with differentially expressed proteins distributed across subcellular compartments such as the cytoplasm, extracellular space, and mitochondria, and enriched in pathways including energy production and conversion. This provides insights into the proteomic basis underlying JPYS's renoprotective effects in CKD.