Introduction and Aims: Detection of podocytes in the urine of patients with Type 2 diabetes mellitus (DM) may indicate severe injury to the podocytes, a main component of the glomerular filtration barrier. Urinary podocytes correlate with disease activity in diabetic nephropathy (DN). To date, the tubular theory concerning the mechanisms of albuminuria in the course of Type 2 DM states that the proximal tubule (PT) is involved in urinary albumin processing. The aim of study was to evaluate a potential association of urinary podocytes with PT dysfunction. Also, we queried whether this association could be related to advanced glycation end-products (AGE) intervention. Methods: A total of 86 patients with type 2 DM (34-normoalbuminuria;30-microalbuminuria; 22-macroalbuminuria) and 28 healthy subjects were enrolled in a cross-sectional study. All patients were assessed concerning urinary albumin:creatinine ratio (UACR), urinary alpha1-microglobulin, urinary kidney injury molecule-1 (uKIM-1), nephrinuria, urinary vascular endothelial growth factor (uVEGF), urinary AGE, and serum cystatin C. Urinary podocytes were examined in cell cultures by immunofluorescence utilizing a monoclonal antibody against podocalyxin, a specific marker expressed on the surface of podocytes. Results: Podocytes were detected in the urine of 10% of the healthy controls and 23.5% of the normoalbuminuric, 40% of the microalbuminuric, and 81.8% of the macroalbuminuric patients, respectively.Podocyturia correlated with urinary alpha1-microglobulin ( p<0.0001), uKIM-1( p <0.0001), UACR ( p<0.0001), nephrinuria ( p<0.0001), uVEGF ( p<0.0001), urinary AGE ( p<0.0001), serum cystatin C ( p<0.001), and eGFR ( p<0.0001). Nephrinuria and uVEGF correlated with UACR ( p<0.0001;p<0.006), urinary AGE ( p<0.0001;p<0.0001), serum cystatin C ( p<0.0006; p <0.0001), and eGFR ( p<0.007; p<0.0001). After adjustment for potential confounders in multivariable regression analysis, urinary podocytes correlated directly with urinary alpha1-microglobulin ( p<0.0001), uKIM-1 ( p <0.0001), UACR ( p<0.0001), urinary AGE ( p<0.0001; p<0.008), nephrinuria ( p<0.001), uVEGF ( p<0.0001), serum cystatin C ( p<0.0001), and indirectly with eGFR ( p<0.007; p<0.001). Conclusions: In patients with Type 2 DM urinary podocytes are found even in the normoalbuminuria stage. There is an association between PT dysfunction and urinary podocytes and their damage biomarkers, nephrin and VEGF. AGE could be involved in podocyturia, as well as in PT dysfunction. Podocyturia may be a useful marker of early DN in conjunction with biomarkes of PT dysfunction.