Background: Reactive oxygen species are believed to contribute to the development of several diseases by causing oxidative stress and oxidative damage. The tryphenylethylene drug Tamoxifen, widely used for breast cancer therapy, demonstrated some serious side effects, among which liver disease and liver cancer (1). We have investigated the effects of acute exposure to high doses of Tamoxifen on the oxidative stress parameters and DNA damage in rat liver. Materials and methods: Female Wistar rats were dosed with Tamoxifen 35 mg/kg body weight and 150mg/kg body weight by oral gavage for 2 days and were humanely killed on the 3rd day of the experiment. Lipid peroxides (2) and protein carbonyls (3), as markers of oxidative stress, and hydrogen donating ability (4), as a measure of non-enzymic antioxidant capacity, were measured in liver homogenates. For assessing the DNA damage, single cell gell electrophoresis (5) was performed on liver cells. All data are presented as mean values *plusmn* SD. The data were analysed using the unpaired Student′s T-test for comparing the groups. The 0.05 level of significance was chosen. Results: The levels of lipid peroxides (LPx) and protein carbonyls (PC) were significantly higher, while hydrogen donating ability (HAD) was lower in the liver homogenate of Tamoxifen treated rats, for both doses, as compared to controls (Tam 35 mg/kg body weight vs. controls LPx t(11)=5.79, p<0.001, PC t(11)=6.43, p<0.001, HAD t(11)=-4.52, p<0.001; Tam 150 mg/kg body weight vs. controls LPx t(11)=7,22, p<0.0001, PC t(11)=6.11, p<0.001, HAD t(11)=-4.69, p<0.001). The tailfactor (TF) and score of lesion (SL) in the comet assay, as a measure of DNA damage, were significantly higher in the study groups as compared to controls, for both doses (Tam 35 mg/kg body weight vs. controls TF t(11)=7.06, p<0.001, SL t(11)=5.42, p<0.001; Tam 150 mg/kg body weight vs. controls TF t(11)=3.24, p<0.01, SL t(11)=3.64, p<0.01). While oxidative stress parameters were similar for both doses of tamoxifen, we found more pronounced DNA lesions in 35 mg/body weight treated animals. Conclusions: Acute exposure to high doses of Tamoxifen produces oxidative stress and DNA damage in female rat liver. The oxidant effects of tamoxifen are similar for the two doses used in the experiment. The DNA damaging effect is more pronounced for the lower dose.