Background: Betamethasone treatment is widely used and recommended worldwide. Although, there are no enough studies to look for the risk or potential alterations due to accumulation of this drug before fertilization. In addition, previous studies payed attention to intramuscular injection during pregnancy neglecting the long-term impact of the use of topical solutions. So, the aim of the present study was to determine this side effect. Methods: We used two doses of betamethasone: 0.02 and 0.2 mg/Kg b.w. were and at the end of the experimental period (after 3 weeks of delivery), six new-born rabbits of both sexes (1 new born rabbit per mother) were dissected under light anesthesia and heart samples were collected. All the measurements were performed in one assay. Result: The results of this study revealed maternal exposure to betamethasone prior to fertilization, induced oxidative stress, alterations in levels of enzymes. Furthermore, these biochemical alterations were supported by histopathological and ultrastructural observations. So, this study suggested that females; desiring to be pregnant, should stop treatment of psoriasis with betamethasone before fertilization to avoid heart toxicity of their offspring.