Oxidative stress is an important contributory factor resulting the development of kidney injury in patients with diabetes. Numerous in?vitro and in?vivo studies have suggested that anthocyanins, natural phenols commonly existing in numerous fruits and vegetables, exhibit important antioxidative, anti?in?ammatory and antihyperlipidemic effects; however, their effects and underlying mechanisms on diabetic nephropathy (DN) have not yet been fully determined. In the present study, the regulation of apoptosis metabolism and antioxidative effects exhibited by anthocyanins [grape seed procyanidin (GSPE) and cyanidin?3?O?β?glucoside chloride (C3G)] were investigated, and the molecular mechanism underlying this process was investigated in?vivo and in?vitro. GSPE administration was revealed to suppress renal cell apoptosis, as well as suppress the expression of Bcl?2 in diabetic mouse kidneys. Furthermore, GSPE administration was demonstrated to suppress the expression of thioredoxin interacting protein (TXNIP), in addition to enhancing p38 mitogen?activation protein kinase (MAPK) and extracellular signal?regulated kinase?1/2 (ERK1/2) oxidase activity in diabetic mouse kidneys. In?vitro experiments using HK?2 cells revealed that C3G suppressed the generation of HG?mediated reactive oxygen species, cellular apoptosis, the expression of cleaved caspase?3 and the Bax/Bcl?2 ratio; and enhanced the expression of cytochrome?c released from mitochondria. Furthermore, treatment with C3G was revealed to suppress the expression of TXNIP, in addition to the phosphorylation of p38?MAPK and ERK1/2 oxidase activity in HK?2 cells under HG conditions. In addition, treatment with C3G was revealed to attenuate the HG?induced suppression of the biological activity of thioredoxin, and to enhance the expression of thioredoxin 2 in HK?2 cells under HG conditions. In conclusion, the present study demonstrated that anthocyanins may exhibit protective effects against HG?induced renal injury in DN via antioxidant activity.