AIM: To investigate the effect and mechanism of panax notoginseng saponins (PNS) inhibiting the proliferation of pulmonary artery smooth muscle cells (PASMCs) in rats under the effect of monocrotaline (MCT). METHODS: PASMCs cultured in vitro were randomly divided into the normal control (Control) group, the monocrotaline (MCT) group, the panax notoginseng saponins (PNS) group, the knockdown (M+Si ADAM10) group, the knockdown postconditioning (M+P+Si ADAM10) group, the overexpression (M+OE ADAM10) group, and the overexpression postconditioning (M+P+OE ADAM10) group. After the model was constructed, the cell viability of each group was measured using the CCK-8 assay, along with Western blot utilized to detect the expression of proliferating cell nuclear antigen (PCNA), disintegrin metalloproteinase 10 (ADAM10), and notch homology protein-3 (Notch3) at the cellular neurogenic locus, respectively. RESULTS：Under the effect of MCT, the viability of PASMCs was significantly enhanced (P<0.05 or P<0.01); 0-400 mg/L PNS was not toxic to the viability of normal cells, and 100 mg/L PNS could significantly inhibit the MCT-induced viability (P<0.01). After the knockdown of ADAM10, the viability of PASMCs significantly declined (P<0.01),and the expression of PCNA protein was significantly decreased (P<0.05), evidently in the M+P+Si ADAM10 group. Meanwhile, the expression of ADAM10 and Notch3 protein was significantly decreased (P<0.05 or P<0.01), evidently in the M+P+Si ADAM10 group. After overexpression of ADAM10, the viability of PASMCs was significantly enhanced (P<0.01), the expression of PCNA protein was significantly increased (P<0.01), the PCNA value was slightly higher (P>0.05), and the expression of ADAM10 and Notch3 protein was significantly elevated (P<0.05) in the M+P+OE ADAM10 group. Additionally, PASMCs overexpressing ADAM10 with concomitant PNS exhibited a significant decrease in the expression of PCNA protein compared with PASMCs knocking down ADAM10 (P<0.01), and the expression of ADAM10 and Notch3 protein declined to varying degrees (P>0.05).CONCLUSION: Panax notoginseng saponins can mitigate MCT-induced PASMCs proliferation in rats by inhibiting the ADAM10/Notch3 signaling pathway.