Objective: To investigate the impacts of microRNA-101-3p (miR-101-3p) on the vascular endothelial growth factor A (VEGFA)/phosphatidylinositol 3-kinase (PI3K)/serine threonine protein kinase (AKT) pathway, inflammatory response, and pregnancy outcomes in rats with hypertensive disorder of pregnancy (HDP). Methods: The expression of miR-101-3p and VEGFA in serum samples of 60 normal pregnant women (control group) and 60 HDP pregnant women (HDP group) who underwent regular prenatal check-up in our hospital from March 2024 to October 2024 were detected by qRT-PCR. The HDP rat model was constructed, and successfully modeled rats were stochastically divided into HDP group, NC antagomir group (tail vein injection of NC antagomir), and miR-101-3p antagomir group (tail vein injection of miR-101-3p antagomir). Another 10 normal pregnant rats were used as the Control group, and equal amounts of physiological saline were injected into both the Control group and the HDP group. The blood pressure, 24-hour urine protein, and pregnancy outcomes of rats in each group were measured. QRT-PCR was used to detect the expression of miR-101-3p in placental tissue of HDP rats. ELISA kit was used to detect the expression of inflammatory factors and vascular injury factors in serum. Western blot was used to detect the expression of VEGFA, PI3K, and AKT proteins in placental tissue. Results: The expression of miR-101-3p was high and VEGFA was low in HDP group (P<0.05).The morphology and structure of placental tissue in the Control group were normal; the placental tissue structure of the HDP group and NC antagomir group was blurred, with a large amount of inflammatory cell infiltration visible; the placental tissue damage and inflammatory cell infiltration of pregnant mice in the miR-101-3p antagomir group were reduced. The blood pressure, 24-hour urinary protein, miR-101-3p, IL-1β, IL-6, TNF-α, sICAM-1, and ET-1 in the HDP group were higher than those in the control group, while the embryo survival rate, NO, VEGFA mRNA and protein, PI3K, and AKT were lower than those in the control group (P<0.05). The blood pressure, 24-hour urinary protein, miR-101-3p, IL-1β, IL-6, TNF-α, sICAM-1, and ET-1 in the miR-101-3p antagomir group were lower than those in the HDP group and NC antagomir group, while the embryo survival rate, NO, VEGFA mRNA and protein, PI3K, and AKT were higher than those in the HDP group and NC antagomir group (P<0.05). Conclusion: Inhibiting miR-101-3p can activate the VEGFA/PI3K/AKT pathway, suppress inflammatory response and vascular damage, and ameliorate pregnancy outcomes.