The present study was to evaluate the hepatotoxicity effects in mice exposed to copper (Cu) used as dietary supplements for 95 days. Cu-treated mice showed increased body weight, and no toxic symptoms were observed at the beginning, but the tendency gradually changed with progress of experiment. In the liver, beneficial metals [Cu, iron (Fe), zinc (Zn), manganese (Mn), and molybdenum (Mo)] were analyzed by flame atomic absorption spectrometry. The content of Cu maintained at the same level during the experiments, but not resulting in the imbalance of Fe, Zn, Mn, and Mo being distributed. The activities of alkaline phosphatase (AKP) and super oxidation dismutase (SOD) showed significantly improvement during the first 30 days in Cu-supplemented group (P<0.01) but declined rapidly from 30th to 60th days, and later, they stabilized and were not statistically significant compared with control (P>0.05). No statistically significant correlation of ceruloplasmin (CPL) activity was appreciated during the experiment. The histopathological and ultrastructural abnormalities changes were observed in the liver of mice including vacuolar degeneration, necrosis, karyorrhexis, and endolysis. Many hepatocytes showed increased collagenic fibers, appearance of triglyceride droplets, and swollen mitochondria due to oral route of copper, which may lead to lipid peroxidation and free radicals. In conclusion, our study showed that exposure to copper influenced behavioral pattern and body weight, affected several enzymatic activities, and led to the physiological and considerable structural changes in the liver of mice. The public should pay more attention to avoid being exposed to copper.