Pulmonary arterial hypertension (PAH), a chronic and progressive disease of the lung vascular system, is characterized by vasculopathy in the pulmonary arterioles, especially in endothelial cells and pulmonary vascular smooth cells. Several mechanisms are involved in PAH occurrence and development, and all are characterized by excessive pulmonary vasoconstriction and abnormal vascular remodeling, which leads to a progressive resistance to blood flow and an increase in pulmonary artery pressure. Recent studies have shown that endoplasmic reticulum (ER) stress is implicated in the pathophysiology of PAH. In this review, we highlight the effect of ER stress on the proliferation and apoptosis of endothelial cells and pulmonary vascular smooth muscle cells, and discuss the feasibility of targeting unfolded protein response components as a strategy to reverse or alleviate the progression of PAH. © 2020 E-Century Publishing Corporation. All rights reserved.