In this study, we found that diabetic mice developed albuminuria, mesangial matrix expansion, tubulointerstitial fibrosis and macrophage influx and showed a decreased renal function; PTPN2 was markedly down‐regulated in diabetic mice, with increased activation of STAT and STAT‐dependent pro‐inflammatory and pro‐fibrogenic cytokines; PTPN2 gene therapy could exert protective effects on DN via ameliorating metabolic disorders and inhibiting renal micro‐inflammation. Here, PTPN2 is linked to metabolic disease.