In general, animal model studies have depicted a relatively complete causal chain for us: high glucose environment/insulin resistance → endogenous Klotho down-regulation → oxidative stress, inflammation and abnormal activation of Wnt/β-catenin pathway → podocyte injury, glomerulosclerosis, interstitial fibrosis → DKD progression; the intervention of exogenous Klotho or Klotho derived peptide can block this chain in different links, so as to delay or reverse the effect of DKD. This evidence concerns the gene KL and diabetic kidney disease.