Placental growth and function are of biological significance in that placental tissue promotes prenatal life and the maintenance of pregnancy. Exposure to synthetic estrogens causes embryonic mortality and placental growth restriction in mice. The aim of the present study was to examine the effects of diethylstilbestrol (DES) on placenta in mice. DES at 1, 5, 10 or 15 µg kg–1 day–1, or 17β-estradiol (E2) at 50 µg kg–1 day–1, was administered orally to ICR mice on days 4 through to 8 of gestation. Expression of ERα, ERβ, ERRβ or ERRγ mRNA in the junctional or labyrinth zone of the placentas on day 13 was assessed using RT-PCR, as well as the embrynic mortality, embryonic and placental weight, histological changes of labyrinth and ultrastructural changes of the trophoblast giant cells (TGCs). Embryo mortalities in the DES 10 and 15 µg kg–1 day–1 groups were markedly increased. No significant changes in embryonic and placental weight were observed in any DES- or E2-exposed groups. Expression of ERα mRNA in the junctional zone with male embryos in the 5 µg kg–1 day–1 group was significantly higher than that in the control, whereas expression was not determined in the 15 µg kg–1 day–1 group. Histological observation revealed that the placentas exposed to DES at 10 µg kg–1 day–1 lacked the developing labyrinth. Ultrastructural observation of the TGCs showed poor rough-surfaced endoplasmic reticulum in the DES 10 µg kg–1 day–1 group. The present data suggest that developmental changes induced by DES may be related to interference with the nutrition and oxygen exchange between mother and embryo or decreased protein synthesis, resulting in a high frequency of embryo mortality. Copyright © 2012 John Wiley & Sons, Ltd.