Our study performed the bioinformatics analysis, EV isolation from BMSCs and identification, co-culture of BMSC-EVs and TGF-β1-induced HK-2 cells, investigation of the downstream factor of KLF6, detection of renal fibrosis-related proteins and construction of animal models, progressively verifying the relationship between miR-181d shuttled by BMSC-EVs and KLF6, and ultimately identifying an evolutionarily miR-181d/KLF6/NF-κB signaling in the inhibition of renal fibrosis in the context of chronic kidney disease. This evidence concerns the gene KLF6 and renal fibrosis.