The aim of this study was to compare the possible protective effects of N-acetylcysteine (NAC), caffeic acid (CAPE) and vitamin E (Vit-E) on doxorubicin-induced hepatotoxicity. Thirty-two male Wistar albino rats, weighing between 250 and 350g were supplied and randomly divided into five groups. Animals in study groups were pretreated with a single dose of doxorubicin (Dox), which was administered intraperitoneally (i.p.). Control group (Group I) was treated with intraperitoneal saline injection. Group II did not received any antioxidant agent after the injection. Group III and Group IV were given CAPE and intraperitoneal vitamin E injection for eight days, respectively. Group V received NAC for eight days. The study was finished after 10 days. Tissue samples were collected from all animals and histopathological examination was performed. There was statistically significant difference between the experiment groups and controls by means of mononuclear cell infiltration and diameters of hepatic sinusoid, terminal hepatic venule (central vein) and portal area (portal canal). Changes related with hepatocellular damage were more prominent, whereas there was no significant difference between Dox and NAC given groups histopathologically. It was observed that structural changes were regressed after CAPE administration. However, this recovery was more prominent in vitamin E given group. These findings suggest that Dox induced liver damage could be efficiently reversed by vitamin E administration. It has been found that CAPE, but not NAC has protective effects on Dox-induced hepatocellular damage.