Ethyl caffeate (CfE, caffeic acid ethyl ester) was extracted from dealcoholized Verdicchio, a white wine from Marche (Italy) with ethyl acetate and then purified with semipreparative reversed‐phase high‐performance liquid chromatography (RP‐HPLC) using an ODS2 column (25 cm×20 mm id) at an isocratic flow of 5 mL/min (the mobile phase A was formic acid 4.5% in water and the mobile phase B was acetonitrile). The CfE extract administered intraperitoneally at 1 μmol/L in rats previously treated with 10 mg/kg dimethylnitrosamine was able to prevent the dimethylnitrosamine‐induced loss in body and liver weight, as well as to reduce the degree of liver injury, as determined by alanine aminotransferase values and necroinflammatory score, after a 1‐week treatment. This was associated with a reduced hepatic stellate cells activation (from 16.8 to 8.3% of smooth muscle actin positive parenchyma) and proliferation (from 11.3 to 5.5 cells/mm2). The collagen synthesis was also reduced: the percentage of Sirius Red positive parenchyma decreased from 21.7 to 7.2%. The CfE levels of Verdicchio wine determined with RP‐HPLC‐DAD were about 14 times the active levels tested in the in vivotest. CfE can be considered as a promising natural compound for future application in chronic liver disease.