Epidemiologic data suggest that non-alcoholic fatty liver disease (NAFLD) have an increased tendency to occur in patients who are associated with metabolic conditions such as obesity, type 2 diabetes mellitus, and dyslipidemia. NAFLD represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign, no-progressive clinical course, to non-alcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end stage liver disease. However, currently the diagnosis of NASH requires an invasive liver biopsy. The aim of this study is to evaluate whether Cytokeratin 18 (CK-18) has potential non-invasive diagnostic capability for the NASH. Serum levels of alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, adiponectin, leptin, and CK-18 were measured in 27 patients (8 patients with simple fatty liver, 6 fatty liver with fibrosis patients, 13 patients with NASH) and 23 healthy controls. Regarding gender difference in the control group, although both adiponectin and leptin significantly increased in the female compared with the male (p < 0.002 and p < 0.01, respectively), there were no significant gender differences in CK-18. For the conventional liver function tests, there were no significant differences in 4 groups. Serum levels of adiponectin was significantly lower in patients with NASH compared with the control group(p < 0.001), and both leptin and CK-18 were markedly higher in patients with NASH compared with control group (p < 0.001). These results suggested that measurement of serum CK-18 is useful for assessing the NASH.