Diabetic nephropathy (DN) is the most common cause of end-stage renal disease. Urinary pigment epithelium-derived factor (PEDF) has also been shown to suppress the expression of fibrogenic, pro-inflammatory, and angiogenic factors, thus contributing to pathological changes in early DN. We aimed to study the role of urinary PEDF as a biomarker for the detection of chronic kidney disease progression in patients with type 2 diabetes mellitus (T2DM). Sixty patients with T2DM were recruited in addition to 20 nondiabetic healthy volunteers. Urinary PEDF using enzyme-linked immunoassay technique was performed to all subjects, and correlations between it and different clinical parameters were examined. Our study showed a statistically significant correlation between urinary PEDF level and duration of DM (P <0.001), glycosylated hemoglobin (P <0.001), serum creatinine (P <0.001), urinary albumin-to-creatinine ratio (P <0.001), and stage of diabetic retinopathy by fundus examination (P <0.001). Urinary PEDF is a good indicator of progression of DN and microvascular damage (as a complication of diabetes) in general. It was also increased in case of poor diabetic control.