Background: Diabetic nephropathy (DN) is the main cause of chronic kidney disease and represents the most common and serious complication of diabetes. An early diagnosis and intervention may slow down disease progression. The diagnosis of diabetic kidney disease (DKD) is based on clinical findings. It is defined by a decrease in GFR, the presence of albuminuria, or the existence of both dysfunctions in a patient with diabetes. A persistent reduction of estimated GFR below 60 mL/min/1.73 m2 and/or the existence of albuminuria (albumin-to/creatinine urine ratio ≥30 mg/g) in two measurements with at least a 3-month difference is sufficient to make a diagnosis of DKD in a patient with diabetes. FGF21, a hormone mainly produced in liver, is induced directly by peroxisome proliferator-activated receptor-α (PPARα). The level of FGF21 in the plasma of diabetic patients significantly increased and was identified as an independent predictor of type 2 diabetes predicting the development of diabetes. Moreover, in type 2 diabetes patients, the level of serum FGF21 is significantly linked to the occurrence of nephropathy, proteinuria, and the progression of end-stage renal disease (ESRD)