Abstract: Diabetic kidney disease (DKD) associated fibrosis represents a central pathological substrate underlying progressive renal function decline. Emerging evidence from gutkidney axis research indicates that disruption of the intestinal barrier and metabolic dysregulation facilitate the translocation of gut-derived pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and microbial metabolites, thereby activating innate immune signaling pathways, including Toll-like receptor 4 (TLR4), the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis. These immune cues promote a T helper 17 (Th17)/regulatory T cell (Treg) imbalance and skew macrophage polarization, which in turn cooperate with profibrotic programs such as transforming growth factor-β (TGF-β)/Smad and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling to drive extracellular matrix deposition. Therapeutic strategies targeting the NLRP3 inflammasome, farnesoid X receptor (FXR)/Takeda G protein-coupled receptor 5 (TGR5), and the gut microbiota have shown potential translational promise. Framed around a cascade model of barrier disruption-immune activationfibrotic execution, this review synthesizes key mechanistic evidence to inform antifibrotic target discovery and the design of future clinical studies.