Objective To explore the relationship between Piezo1 and IL-6 secretion in rat pulmonary artery fibroblasts and clarify the mechanism of Piezo1 channel in the development of pulmonary arterial hypertension.Methods Pulmonary artery tissue of adult SD rats was obtained and pulmonary artery fibroblasts were isolated and cultured through tissue block method. The cells were divided into control group and fluid shear force group. The fluid shear force system was used to culture the fluid shear force group cells for 24h under the condition of 12dyn/cm2, and no additional treatment was done in the control group. The levels of Piezo1 protein and mRNA in the control group and the fluid shear force group were detected by Western blot and PCR. Pulmonary artery fibroblasts was divided into the PBS group, Yoda1 and Yoda1+Dooku1 group, and add 10 μM PBS, Yoda1 and Yoda1+Dooku1 respectively. After 24 hours of cultivation, the IL-6 protein and mRNA level in each group was measured; Yoda1 group cell was divided into four groups and PBS (10 μl), ERK inhibitor (PD98059, 10 μM), JNK inhibitor (SP600125, 10 μM)and p38 MAPK inhibitor (SB203580, 5 M), and the IL-6 mRNA level was measured 24h after the treatment. The level of p-p38 MAPK protein was detected in PBS group, Yoda1 group and Yoda1+Dooku1 group 10min after the treatment. Results Pulmonary artery fibroblasts were isolated and cultured successfully. After a 24h culture in 12dyn/cm2 fluid shear force condition, both Piezo1 protein and mRNA levels were significantly increased in the fluid shear force group compared with the control group (P＜0.05)After a 24h cell culture in PBS group, Yoda1 group and Yoda1+Dooku1 group, IL-6 protein and mRNA levels in Yoda1 group were significantly increased compared with PBS group and Yoda1+Dooku1 group (P＜0.05) However, there were no significant differences in IL-6 protein and mRNA levels in Yoda1+Dooku1 group compared with PBS group (P＞0.05) PBS, ERK inhibitor, JNK inhibitor and p38 MAPK inhibitor were added into Yoda1 group and cultured for 24h. Compared with PBS, ERK inhibitor and JNK inhibitor groups, IL-6 mRNA level in the p38 MAPK inhibitor group was inhibited and significantly decreased (P＜0.05)However, there was no significant difference in IL-6 mRNA level between PBS group, ERK inhibitor group and JNK inhibitor group (P＞0.05)Phosphorylated p38 MAPK level in PBS group, Yoda1 group and Yoda1+Dooku1 group showed that compared with the PBS group, the phosphorylated p38 level in Yoda1 group was significantly higher than that in PBS group (P＜0.05), and there was no significant difference in phosphorylated p38 in Yoda1+Dooku1 group (P＞0.05) Conclusion The expression of Piezo1 can be up-regulated and activated in pulmonary artery fibroblasts, bring a Ca2+ flow and activating the p38 MAPK pathway, to promote IL-6 secretion. It leads to vascular remodeling and accelerate the process of pulmonary hypertension