Abstract: As of this writing, the most common cause of hepatic fibrosis is chronic hepatitis C virus infection (HCV), the characteristic feature of which is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which in turn activates hepatic stellate cells (HSCs). HSCs are also thought to be the primary target cells for inflammatory stimuli, and produce extracellular matrix components. Based on available clinical information, chronic hepatitis C appears to progress more rapidly in men than in women, and cirrhosis is predominately a disease of men and postmenopausal women. It should be noted that estradiol (E2) is a potent endogenous antioxidant. A recent study has shown that hepatic steatosis became evident in an aromatase-deficient mouse and was diminished in animals, after treatment with E2. Our studies showed that E2 suppressed hepatic fibrosis in hepatic fibrosis models, inhibited the activation of activator protein 1 and nuclear factor-κB in cultured hepatocytes undergoing oxidative stress, and attenuated HSC activation in primary culture. Recently, variant oestrogen receptors (ERs) were found to be expressed to a greater extent in male patients with chronic liver disease than in female subjects. We also demonstrated decreased levels of ERs in postmenopausal women and cirrhotic patients of both genders. The actions of E2 are mediated through ER α and β. HSCs have also been found to possess functional ER β but not ER α. A better understanding the basic mechanisms underlying the gender-associated differences observed in the development of hepatic fibrosis would provide valuable information relative to the search for effective antifibrogenic therapies.