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Objective Too investigate the plasma level of CD248 in patients with pulmonary arterial hypertension (PAH) and its clinical significance. Methods A total of 30 PAH patients, including 14 with idiopathic pulmonary arterial hypertension (IPAH) and 16 with chronic thromboembolic pulmonary hypertension (CTEPH) who were diagnosed by right heart catheterization in the our department from March 2016 to June 2019 were recruited, and 12 healthy individuals who taking physical examination during same period served as control group in this study. Plasma levels of CD248 protein in healthy controls and PAH patients were detected using ELISA. After monocrotaline (MCT) was used to induce PAH in SD rats, and the level of CD248 in rat plasma was also detected by ELISA. Then in vitro, after rat pulmonary artery smooth muscle cells (PASMCs) were isolated and identified and then cultured to passages 5~7, they were treated with TNF-α or platelet-derived growth factor-BB (PDGF-BB), and the mRNA expression of CD248 in the cells was measured with qPCR. Results The plasma level of CD248 was significantly lower in the PAH patients than the healthy controls (P < 0.01). Its area under the curve (AUC) of the receiver operating characteristic (ROC) curve for PAH was 0.79 (95%CI: 0.64~0.94, P < 0.01). Similarly, the level of CD248 in the plasma of rats was lower in the MCT treatment group than the control group. After the intervention of PDGF-BB, the mRNA level of CD248 in PASMCs was first up-regulated and then down-regulated. Conclusion CD248 is lowly expressed in the plasma of PAH patients, and it has the potential to be used as a biomarker to assist in the diagnosis of PAH.