ABSTRACT Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is emerging as an independent cardiovascular risk factor. Recently, Endocan has been studied as an early marker of endothelial dysfunction. Our aim was to evaluate Endocan serum levels in patients with NAFLD with or without type 2 diabetes mellitus. Method: We enrolled 56 patients: 19 with NAFLD and 37 with type 2 diabetes mellitus with or without NAFLD, and compared them to 25 healthy controls. Endocan serum level was measured by using the ELISA EndoMark assay. Results: Endocan level was significantly higher in NAFLD subjects, compared to controls (1.23±1.51 vs 0.68±0.4 ng/mL; p=0.016). It was higher in patients with non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH) (1.12±1.11, 1.49±2.16 and 0.68±0.4 ng/ml vs controls, respectively), independently from presence of type 2 diabetes mellitus. The increase was more marked in patients with NASH and in those with NAFL versus controls (p=0.001 and p=0.004, respectively), but not statistically different between the two groups (p=0.448). Finally, we found a statistically relevant increase of this marker in diabetic NAFLD patients compared to those non diabetic (1.56±0.81 vs 0.72±0.58 ng/ml; p=0.01). Conclusion: We demonstrated an increased Endocan serum level in NAFLD patients, higher in those with type 2 diabetes mellitus and/or NASH because of an endothelial dysfunction in these pathologies. Key words: Endocan – Non Alcoholic Fatty Liver Disease – Type 2 diabetes mellitus. Abbreviations: BMI: Body Mass Index; CCBS: calcium channel blockers; ED: endothelial dysfunction; ELISA: enzyme-linked immunosorbent assay; ESM-1: Endothelial cell-specific molecule-1; HOMA-IR: Homeostasis Model Assessment Insulin Resistance; ICAM: Intercellular Adhesion Molecule; LFA-1: Lymphocyte Function-Associated Antigen 1; NAFL: non-alcoholic fatty liver; NAFLD: Non-alcoholic fatty liver disease; NAS: non-alcoholic fatty liver disease activity score; NASH: non-alcoholic steatohepatitis; ROS: reactive oxigen species; T2DM: type 2 diabetes mellitus; TNF-alpha: tumor necrosis factor-alpha.