Objective(s): Non-alcoholic steatohepatitis (NASH) is a chronic liver disease with unknown etiology. The insulin resistance, immune mechanisms and oxidative stress are the main factors in its pathogenesis. Dipeptidyl peptidase IV (DPPIV) or CD26 is a protein with endocrine and immune functions. This study aimed to elicudate the changes related to DPPIV in NASH patients. Methods: Serum and urinary DPPIV activities were measured in 31 NASH patients and 17 healthy controls. The liver biopsies of 29 patients were immunolabeled for CD26. Results: The mean age of patients were 46 +/- 11 years and 14 (45%) of them were female. The serum DPPIV activity was higher in patients (57.3 +/- 7.8 U/L) than controls (43.6 +/- 10.6 U/L) (p < 0.0001), and correlated with the histopathological grade (p = 0.038, r = 0.373) and hepatosteatosis (p = 0.018, r = 0.423) but not with stage (p = 0.286), class (p = 0.286) or CD26 staining (p = 0.743). The urinary DPPIV activity was similar in patients (1.52 +/- 0.94 U/mmol creatinine) and controls (1.37 +/- 0.68 U/mmol creatinine) (p = 0.861). Three acinar zones of liver had equal CD26 expression (p = 0.076). The intensity of CD26 immunostaining was correlated with histopathological grade (p = 0.001) and hepatosteatosis (p = 0.003) but no correlation with stage or class could be detected (p = 0.610 and 0.956, respectively). In Conclusions: The serum DPPIV activity and the staining intensity of CD26 in liver are correlated with histopathologic grade of NASH and hepatosteatosis. DPPIV can be proposed as a novel candidate with several potential functions in NASH pathogenesis.