Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a disease gaining increasing interest worldwide. It ranges from simple nonalcoholic steatosis to nonalcoholic steatohepatitis (NASH), is characterized by steatosis, inflammation and fibrosis, and may lead to liver cirrhosis and hepatocellular carcinoma. Nonalcoholic fatty liver disease shares common pathogenetic mechanisms with other components of the insulin resistance or metabolic syndrome, with adipokines playing a crucial role. Aim of the Work Recent studies suggest that activin A, a member of the transforming growth factor (TGF) superfamily, is involved in the pathogenesis of liver disorders. We sought to explore its possible role in non-alcoholic fatty liver disease (NAFLD). Patients and Methods This study is a comparative case control study. This study was carried out at outpatient’s clinics of internal medicine department of Ain Shams University. Target population Group 1: Including 35 patients with NAS (steatosis) with exclusion criteria of intake of hepatotoxic drugs. Group 2: Including 35 patients with fatty liver and elevated liver enzymes (NASH). Group 3: Including 20 patients as a control group. Results There was high statistically significant difference between the studied groups as regard weight and BMI. In the Steatosis group the mean Liver size was 13.97 (±1.29 SD) with range (1216) cm, all the patients (100%) had enlarged- echogenic liver. In the NASH group the mean Liver size was 13.71 (±1.36 SD) with range (12-16) cm, all the patients (100%) had enlarged-echogenic liver. In the control group the mean Liver size was 9.85 (±1.5 SD) with range (8-12) cm, all the patients (100%) had Normal liver. There was high statistically significant difference between the studied groups as regard liver size. There was high statistically significant difference between the studied groups as regard ALT, AST, total and direct bilirubin, plts count and activin A, significant difference between the studied groups as regard Albumin. There was high statistically significant difference between the studied groups as regard APRI score, FIB-4. There was high correlation between Activin A and BMI, APRI score, FIB-4 and liver size with high significance (p < 0.001). Using Activin A. it was shown that above 858.5, it can discriminate between NAFLD and nonNAFLD with level of sensitivity 100% and specificity 100%. Conclusion Serum activin A showed a trend towards progressive increase from controls, to SS and NASH patients, but the significance was lost after adjustment for measures of adiposity. Activin A was not independently associated with NASH or any specific hepatic lesion within NAFLD patients. Prospective studies are needed to confirm the hypothesis raised herein, before mechanistic studies attempt to elucidate mechanism and prove causality.