Background: Albumin in the urine is an indicator of diabetic nephropathy (DN), a serious kidney condition brought on by destruction to the kidney's glomerular blood capillaries. In diabetic kidney disease (DKD), it was previously thought that albuminuria happens before kidney function declines. However, new epidemiological investigations showed that a subset of cases had kidney failure without albuminuria. It has been proposed that additional glomerular and/or tubular damage biomarkers can predict early renal failure and structural abnormalities, even prior to the onset of microalbuminuria.This study aimed to evaluate the role of fibroblast growth factor21 (FGF21) and fibroblast growth factor23 (FGF23) in early diagnosis of diabetic nephropathy in type 2 diabetes mellitus (T2DM) patients. Methods:This case control investigation recruited 66 subjects allocated into three groups: 22 apparently healthy subjects as control group, 22 T2DM cases with normoalbuminuria and 22 T2DM cases with microalbuminuria. Serum FGF21 and FGF23 were assayed by ELISA. Results: Serum FGF21 and FGF23 were substantially increased in patients with microalbuminuria compared to normoalbuminuric patients and control group. There was a significant positive correlation between FGF21 and FGF23 and between each of them with HbA1c, blood urea nitrogen (BUN), urine albumin creatinine ratio (UACR), and creatinine. A significant negative correlation was detected between both FGF21 and FGF23 and estimated glomerular filtration rate (eGFR). The sensitivities of FGF21 and FGF23 in predicting DN were 72.73% and 86.3% respectively. The specificities were 86.3% and 72.73% respectively. When combining both markers, the sensitivity was 86.3%. Conclusion: FGF21 and FGF23 were significantly elevated in T2DM patients and in T2DM patients with microalbuminuria compared to those with normoalbuminuria. They can be considered promising markers for diagnosis of early stage of DN in T2DM patients