Despite being one of the leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of preeclampsia are unknown. The initiating event in preeclampsia has been postulated to be reduced uteroplacental perfusion. Placental ischemia/hypoxia is thought to lead to widespread activation/dysfunction of the maternal vascular endothelium, vasoconstriction and hypertension. Experimental induction of chronic uteroplacental ischemia appears to be the most promising animal model to study potential mechanisms of preeclampsia since reductions in uteroplacental blood flow in a variety of animal models lead to a hypertensive state that closely resembles preeclampsia in women. This chapter details the methods we use in our laboratory to produce the reduced uterine perfusion pressure (RUPP) model in the pregnant rat.