Abstract Body: Introduction: Preeclampsia (PreE) is characterized by new onset hypertension after 20 weeks of gestation. PreE is associated with activated CD4+ T cells, inflammation, autoantibodies to angiotensin II type 1 receptor (AT1-AA) and hypertension. To date, the best treatment remains early delivery of the feto-placental unit. Hypothesis: This study was designed to test the hypothesis that progesterone, in the form of 17-hydroxyprogesterone caproate (17-OHPC), reduces inflammation and blood pressure in the Dahl Salt-Sensitive (Dahl S) rat model of PreE. Methods: A subset of pregnant Sprague-Dawley (SD) and Dahl S rats were injected with 17-OHPC (3.32mg/kg, human dose equivalent) or vehicle (saline) at day 15 (GD15) of gestation. On GD 18, Uterine Artery Resistance Index (UARI) was measured by Doppler Ultrasound and carotid catheters were inserted for mean arterial blood pressure (MAP) measurement on GD19. Circulating and placental populations of CD4+ T cells were quantified by flow cytometry. TNF-alpha and IL-6 were measured by ELISA and AT1-AA were quantified by the chronotropic responses to angiotensin II type 1 receptor-mediated stimulation of cultured neonatal rat cardiomyocytes. Results are reported as means ± standard error means (SEM) and statistically significant when p < 0.05. Results: MAP was 105+5 mmHg in SD+ vehicle rats (n=6), 104+4 in SD+17-OHPC rats (n=6), 136+3 in Dahl S+ saline rats (p <0.05, n=11), which improved to 125+4 in DS+17-OHPC rats (p <0.05, n=7). Pup and Placenta weights were 2.1+ 0.1, 0.6 + 0.1 g in SD+ vehicle rats and reduced to 1.4+0.1 (p<0.05), 0.5+0.1 g in Dahl S +vehicle. UARI was 0.5 +0.1 in SD+ vehicle rats (n=6) and 0.5 +0.1 in in SD+17-OHPC (n=6), 0.7+0.1 in Dahl S+ vehicle rats (n=6, p<0.05), which reduced to 0.5+0.1 in Dahl S+17-OHPC (n=7, p<0.05). TNF-alpha and IL-6 levels (n=4-5/group) were 3.0+1.0, 45+11 pg/mL in SD+ vehicle rats, 11.0+1.2, 78+21 in Dahl S+ vehicle rats, which reduced to 4.1+1.6 (p<0.05), 62+12 in Dahl S+17-OHPC. Circulating and placental CD4+ T cells were 9.3+3.7 %, 6.4+ 1.6 % gate in SD+ vehicle rats (n=4), 38.9 +2.9, 33.1+4.3 % gate Dahl S+ Saline rats (n=6), which significantly reduced to 26.3 + 0.1 %, 3.4+1.2 % gate in DahlS+17-OHPC. AT1-AA were -1 + 2 ΔBPM (beats per minute) in SD+ vehicle rats, 4 + 1 in Dahl S+ Saline rats and -0.6+2 Dahl S+17-OHPC rats (n=5, p<0.05). Conclusion: Our findings demonstrate that 17-OHPC ameliorates the maternal syndrome in the Dahl Salt-Sensitive rat model of PreE.