Objective: Doxorubicin (DOX), one of the chemotherapeutic drugs utilized in cancer treatment, has limited clinical use due to its serious toxic effects on non-target organs. The purpose of this study is to reveal the harmful effects of DOX in rat liver and the possible protective effect of propolis (PRPLS), a mixture of various herbal products collected by honeybees, on these damages by Attenuated Total Reflection-Fourier Transformation Infrared (ATR-FTIR) spectroscopy. Methods: Sprague dawley rats were separated into 4 groups; control, DOX (cumulative dose: 15 mg/kg), PRPLS (200 mg/kg) and DOX + PRPLS. The rats were given 200 mg/kg PRPLS by oral gavage daily for 20 consecutive days and 2.5 mg/kg DOX intraperitoneally on days 10, 12, 14, 16, 18 and 20 of the experiment. 24 hrs after the last administrations, liver samples were collected and examined by ATR-FTIR spectroscopy. Results: DOX caused a decrease in the amount of glycogen and nucleic acids, an increase in the amount of lipids and proteins and some important changes in the metabolism, structure and conformation of these molecules in the liver. DOX also induced lipid peroxidation, an increase in membrane fluidity, a decrease in membrane order and protein denaturation. PRPLS did not induce any toxic effect on the liver when it was given alone and PRPLS administered before DOX was not effective to eliminate these harmful effects of DOX. Conclusions: DOX caused significant structural and compositional changes in liver tissue and PRPLS was inadequate to prevent these changes at the dose and time used here.