Abstract Body: Introduction: Despite considerable research over the last few decades, molecular mechanisms that govern preeclamptic (PE) pathogenesis are poorly understood. Recent studies focussed on mechanistic exploration documented that microRNAs (miRNAs) regulate critical processes (endothelial dysfunction, inflammation, oxidative stress) pertinent to PE pathology. However, to the best of our knowledge, a complete placental miRNA expression profiling has not been undertaken. Given the complexity surrounding miRNA biology, a comprehensive miRNA profiling would greatly aid our efforts in better understanding PE pathology. Objective: The objective of the current study was to perform a comprehensive profiling of placental miRNAs in PE rat (reduced perfusion pressure;RUPP) model, and identify their functional relevance. Methods: RUPP surgery was performed on gestational day (GD)14. Blood pressures (carotid catheterization) were collected on GD19, and placenta (~5mg) was used to isolate miRNA (Qiagen’s miRNeasy Micro Kit). Small RNA sequencing (s-RNA seq) was performed by Illumina sequencer(NEXTFLEX Kit). Enrichment analysis was performed using Cytoscape(BINGO, overrepresentation, p=0.05). Functional associations were retrieved using TAM2.0. Results: RUPP rats showed higher MAP (123.8±1.51 vs.98.70±1.53 mmHg, n=10, p<0.0001) vs.control rats. S-RNA seq revealed a total of 142 (40 up and 102 down) differentially regulated (diff-reg) miRNAs in RUPPs. Of these, the top 5 diff-reg miRNAs were; miR-211-3p, miR-628, miR-6324, miR-363-5p, miR-6329 (up) and miR-3587, miR-29b-3p, miR-3556a, miR-29a-3p, miR-21-3p (down). Interestingly, TAM2.0 revealed that these miRNAs are involved in immune response (miR-363, miR-21, miR-29), B-cell differentiation (miR-628), T-cell activation (miR-21), adipogenesis, lipid metabolism (miR-211, miR-29, miR-21), and angiogenesis (miR-363, miR-21) all of which are relevant to PE. Further, enrichment analysis revealed that the top 10 significantly enriched terms include, regulation of transport, cell-cell signaling, calcium ion-dependent exocytosis (BP); synaptic vesicle, perinuclear region of cytoplasm, membrane bound/clathrin-coated vesicle (CC); glycoprotein binding, protein dimerization activity, myosin head/neck binding (MF). Conclusions: Our findings demonstrate that dysregulated placental miRNAs may be involved in PE pathogenesis. Future studies building on these preliminary findings may help identify candidate miRNA for therapeutic manipulation.