: Diabetic kidney disease (DKD) is the most prevalent cause of chronic kidney disease, Due to decreased sensitivity of microalbuminuria for early detection of DKD, there is new shift to other markers for early detection and prediction of DKD and to delay or prevent the development of end stage renal disease. To evaluate fibroblast growth factor 21(FGF21) as an early marker of diabetic kidney disease. 176 participants were involved and divided into 4 groups; group I comprised 44 healthy volunteers, group II comprised 44 patients with type 2 diabetes with normoalbumiuruia, group III comprised 44 patients with type 2 diabetes with microalbuminuria and group IV comprised 44 patients with type 2 diabetes with macroalbuminuria. All participants were submitted to detail clinical examination, laboratory investigations, complete blood count, urine analysis, fasting blood glucose (FBG), random blood glucose (RBG), glycated haemoglobin (HbA1c), serum creatinine, eGFR, albumin creatinine ratio (ACR), lipid profile and serum FGF21 levels assays. FGF21 levels were significantly higher in albuminuria groups than diabetic with normoalbuminuria and control groups. FGF21 was positively correlated with duration of diabetes, FBG, RBG, HbA1C, s.creatinine, ACR, total cholesterol (TC) and triglycerides (TG). At cutoff value more than 492pg/ml, FGF-21 yielded 82.2% sensitivity and 89.1% specificity for the differentiation of microalbuminuria. Serum FGF21 could be used as an early marker for diagnosis and identifying DKD.