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 levels of miR-101-3p, VEGFA, PI3K, and AKT in serum samples of 60 normal pregnant women (control group) and 60 pregnant women with HDP (HDP group) who underwent a regular prenatal check-up at our hospital from March to October 2024 were detected by RT-qPCR. An HDP rat model was constructed, and successfully modeled rats were randomly divided into HDP, NC antagomir (tail vein injection of NC antagomir), and miR-101-3p antagomir groups (tail vein injection of miR-101-3p antagomir). Ten normal pregnant rats were used as the Control group, and equal amounts of physiological saline were injected into the Control and HDP groups. Blood pressure, 24-hour urine protein, and pregnancy outcomes were evaluated in each group. RT-qPCR was used to detect the expression of miR-101-3p,VEGFA,PI3K,and AKT in placental tissues of HDP rats. ELISA was used to detect the expression of inflammatory and vascular injury factors in serum. Western blot was used to detect VEGFA, PI3K, and AKT in placental tissue. A dual-luciferase reporter gene assay verified the interaction between miR-101-3p and VEGFA. Results The expression of miR-101-3p was high, while VEGFA, PI3K, and AKT levels were low in the 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 substantial inflammatory cell infiltration. 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 levels in the HDP group were higher than those in the control group, while the embryo survival rate, NO, VEGFA mRNA and protein, PI3K mRNA and protein, and AKT mRNA and protein levels 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 levels were lower, while the embryo survival rate, NO, VEGFA mRNA and protein, PI3K mRNA and protein, and AKT mRNA and protein levels were higher in the miR-101-3p antagomir group than in the HDP and NC antagomir groups (P<0. 05). miR-101-3p can negatively regulate VEGFA. Conclusions Inhibiting miR-101-3p can activate the VEGFA/ PI3K/ AKT pathway, suppress the inflammatory response and vascular damage,and improve pregnancy outcomes.