Abstract Background and Aims Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) and affects more than 40% of patients with type 2 diabetes mellitus (T2D). The pathogenesis of CKD is multifactorial and leads to a clinical presentation with diverse phenotypes characterised by proteinuria and/or progressive deterioration of renal function, thus urging the search for new non-invasive biomarkers that allow early diagnosis and the development of new therapeutic targets. Urinary extracellular vesicles (EVs) have emerged as an alternative, as changes in their number and composition have been described in clinical conditions associated with DM and kidney disease. EVs are able to interact with neighbouring and/or distant cells by transferring their cargo, rich in proteins, lipids or nucleic acids, from progenitor cells to recipient cells, thus participating in cell-to-cell communication processes. The aim of the present study was to analyse the different phenotypes of EVs in T2D patients with different degrees of albuminuria compared to healthy controls, as well as their correlation with the degree of albuminuria. Method A cohort of 69 subjects (49 patients with T2DM and 20 healthy volunteers) was analysed. The phenotype of EVu present between the two groups was assessed, as well as the association between the different cell lines and the presence of albuminuria. Statistical analysis was performed using Spearman correlations. Analyses were performed with R software. Results A positive correlation was observed between EVu from podocytes (PODO+) and those from macrophagocytes (R = 0.3180, p-value = 0.0082), as well as a positive association between PODO+ and neutrophil EVu, both in the whole cohort and when analysing only patients with diabetes (R = 0.3225, p-value:0.0254). When assessing the association of EVu with the degree of albuminuria, we observed a direct association with proximal tubule EVu (R: 0.3158, p-value 0.0271) both in all subjects (T2D and HV) and only in those with T2D (R = 0.4200, p-value = 0.0056). When stratifying according to the degree of albuminuria (A1, A2 and A3), we still observed a dependent association of the degree of glomerular involvement with the number of EVu of TCP (A1: mean 5.5 (SD 4.1); A2: mean 12.3 (SD 30.9); A3: mean 132.5 (SD 322.8)) p-value: 0.0609. Conclusion The results presented suggest a relevant role of TCP in the glomerular involvement of patients with DKD, in line with the emergence of new therapeutic lines such as iSGLT2. The study suggests new lines of research aimed at developing therapeutic targets that assess the cellular expression of EVu.