Notoginsenoside R 1 , the main active ingredient of Panax notoginseng saponins (PNS), has been proposed to play fatal roles in the development of hypoxic hypercapnia-induced pulmonary vasoconstriction (HHPV). Subsequently, pulmonary arterial smooth muscle cells (PASMCs) lead to pulmonary vascular system remodeling and chronic pulmonary disease in the development of HHPV. Despite considerable studies have contributed to pulmonary disease, the mechanism of how Notoginsenoside R 1 affects HHPV remains unclear. In this view, we will discuss the effect of notoginsenoside R 1 by investigating the expression of p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway in PASMCs under hypoxia and hypercapnia condition. The third order PASMCs of Sprague Dawley (SD) rats were cultured with various concentrations (8, 40, 100 mg/L, respectively) of Notoginsenoside R 1 . Our data showed that the protein and mRNA expression levels of p-38 MAPK were higher in hypoxic hypercapnia group compared with hypoxic DMSO and normoxia control groups (p < 0.01). In R 1 treatment groups, the level of p-p38 MAPK protein and p38 MAPK mRNA were significantly decreased with different degrees (p < 0.01, each). This study provides the evidence that Notoginsenoside R 1 treatment may contribute to attenuate HHPV via decreasing the protein and mRNA expression levels of p-38 MAPK.