The protective effects of OPC and its possible mechanism in preventing the progression of DN were investigated using a multidimensional approach, including its ability in regulating oxidative-antioxidative status (lipid peroxidation, protein carbonyl, superoxide dismutase, and glutathione GST, GSH-Px), metal-binding ability (Cd levels in the kidneys and urine and MT content) and mediation of essential elements (Zn, Ca, Cu, and Fe levels in the kidneys), and activation of the p38 MAPK and Keap1/Nrf2 signaling pathways. Here, KEAP1 is linked to liver dysplastic nodule.