This research studied the effect of polyethylene (PE), Butylated Hydroxytoluene (BHT), PE with BHT, and the thermally-treated PE on the histopathological examination and some biochemical activities of the liver of adult male mice.105 mice were divided into 5 groups. The (PE group) supplied with 20% crushed PE, the (BHT group) supplied 400mg/kg of BHT dissolved in corn oil, the (PE + BHT group) were fed with 20% crushed PE and 400mg/kg of BHT dissolved in corn oil, the (thermally treated PE group) supplied food with 20% of crushed thermally-treated PE, and the control group.  The weight of the mice was recorded before the study and after 6 weeks. Blood samples were collected to determine the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The animals were sacrificed; the liver was weighed before and after treatments and examined microscopically. Liver specimens were stained and examined by a light microscope. The results showed that the mean weights of the mice in PE, BHT, and PE + BHT groups were statistically reduced and the mean weights of their livers significantly (p≥0.05) increased and the enzymes AST and ALT in the blood significantly (p≥0.05) increased in comparison to the control group. The histopathological examination of the liver specimens showed significant changes with all PE and BHT treatments. The results of the current investigation suggest preventing the use of plastic in food preservation and replacing it with safe grade substance like wood materials