Herein, we focused on the upstream signaling of NF-kB signaling-mediated inflammatory pathway, PI3K/Akt signaling, and found that the persistent hyperglycemia activated PI3K/Akt pathway, which promoted the activation of NF-кB signaling and the release of inflammatory cytokines, subsequently leading to massive proteinuria, tubulointerstitial inflammatory infiltration, mesangial matrix expansion and basement membrane thickening in DKD rats. The gene discussed is AKT1; the disease is Hyperglycemia.