【Abstract】 Objective To explore the effect and significance of JAK2/STAT3 pathway inhibitor AG490 and DNA methylation inhibitor 5-Aza on proliferation of rat pulmonary artery smooth muscle cells (PASMCs) induced by platelet-derived growth factor-BB (PDGF-BB). Methods CCK8 was used to detect the effects of different concentrations of AG490 and 5-Aza on PDGF-BBinduced proliferation of PASMCs. The cells were divided into 5 groups, control group: normal PASMCs, 0μM group: 30ng/mL PDGF-BB incubation for 48h, 25μM (1μM), 50 μM (3 μM), 100 μM (5 μM) groups: 25 μm/L AG490 (5-Aza) was co-incubated with 25 (1), 50 (3), 100 (5) on the 0 μM group. RT-qPCR was used to detect the expression of IL-6, GATA6, JAK2 and STAT3 mRNA. Western blot was used to detect the expression of GATA6, p-JAK2 and p-STAT3 protein. Results Compared with the control group, the proliferation of PASMCs was significantly increased after 30 ng/mL PDGF-BB induction, IL-6, JAK2, and STAT3 mRNA expressions increased, GATA6 mRNA levels decreased, p-JAK2/JAK2 and p-STAT3/STAT3 expression increased, and GATA6 protein levels decreased (P＜0.05). AG490 and 5-Aza can inhibit PDGF-BB-induced proliferation of PASMCs, with IC50 of 61-269 μmol/L and 3.507 μmol/L, respectively. Compared with the 0μM group, the expression of IL-6, JAK2 and STAT3mRNA in 25, 50 and 100μM groups were all reduced, GATA6mRNA level was increased, p-JAK2/JAK2 level was decreased, GATA6 protein level was increased, and p-STAT3/STAT3 level was decreased in 50 and 100μM groups (P＜0.05). IL-6 mRNA and p-JAK2/JAK2 levels decreased in 25μM, 50μM, and 100μM groups, p-STAT3/STAT3 and GATA6 protein levels increased, and GATA6 mRNA expression increased in 50μM and 100μM groups (P＜0.05). Conclusion AG490 and 5-Aza have an inhibitory effect on PDGF-BB-induced proliferation of PASMCs, which may be related to blocking the JAK2/STAT3 signaling pathway and inhibiting IL-6 from regulating GATA6 promoter methylation.