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Background In this study, we investigated the effects of treatment with chronic antihypertensive drugs (clonidine, methyldopa, amlodipine, ramipril and rilmenidine) on oxidant-antioxidant parameters and toxic effects on DNA in rat uterus tissue. In addition, uterus tissues were examined histopathologically. Materials and Methods A total of 36 albino Wistar rats were divided into the following six groups: 0.075 mg/kg clonidine group; 100 mg/kg methyldopa group; 2 mg/kg amlodipine group; 2.5 mg/kg ramipril group; 0.5 mg/kg rilmenidine group; and the healthy group. Rats underwent chronic drug administration for 30 days and at the end, biochemical and histopathological examinations were performed. All data were subjected to one-way ANOVA test. Results We divided these drugs into the following three groups according to their effects on rat uteri: (I) mild negative effects (clonidine), (II) moderate negative effects (rilmenidine, methyldopa) and (III) drugs which had severe negative effects (amlodipine, ramipril). Conclusion These data may help with selection of antihypertensive drugs, in order to determine which drugs have the lowest toxicity in pregnant and non-pregnant (pre-pregnancy) women.