Objective: To investigate whether Codonopsis pilosula polysaccharides (CPP) alleviate acute pulmonary embolism (APE) via suppression of inflammation-mediated immune responses. Methods: Sixty 6-month-old healthy SD rats, half male and half female, were randomly divided into five groups: sham operation group, model group, high-dose Codonopsis pilosula polysaccharide group(200 mg·kg^-1·d^-1), medium-dose Codonopsis pilosula polysaccharide group (100 mg·kg^-1·d^-1), low-dose Codonopsis pilosula polysaccharide group (50 mg·kg^-1·d^-1). The rat model of pulmonary embolism was established by internal jugular vein injection of autologous thrombus. The success of model preparation was comprehensively judged by observing daily behavior, combined with blood oxygen saturation detection, D-dimer (D-D) level detection and high-sensitivity C-reactive protein (hs-CRP) level detection. Different doses of Codonopsis pilosula polysaccharide were given to the model animals for 1 week. The daily behavior of the animals was observed and the blood oxygen saturation was detected. The serum levels of hs-CRP, homocysteine (Hcy), D-dimer, thromboxane A2 (TXA2) synthase and prostacyclin (PGI2) synthase were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression levels of D-dimer and plasminogen activator inhibitor-1 (PAI-1) in lung tissue of rats were detected by Western blot. The levels of plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by radioimmunoassay. Results: After modeling, the number of dyspnea, abdominal breathing and alar agitation in the experimental rats were increased (P＜0.05), and the heart rate and blood oxygen saturation were decreased (P＜0.05). Compared with the model group, the abdominal respiration and nasal alar agitation in each dose group of Codonopsis pilosula polysaccharide were decreased (P＜0.05), and the heart rate and blood oxygen saturation in each dose group of Codonopsis pilosula polysaccharide were increased (P＜0.05). ELISA results showed that compared with the sham operation group, the levels of serum hs-CRP, Hcy, TXA2 synthetase and PGI2 synthetase in the model group were increased (P＜0.05). Compared with the model group, the levels of serum hs-CRP, Hcy and TXA2 in each dose group of Codonopsis pilosula polysaccharide were decreased (P＜0.05), and the level of PGI2 was increased (P＜0.05) in a dose-dependent manner. The results of Western blot showed that the protein expression of D-D and PAI-1 in the model group was higher than that in the sham operation group (P＜0.05). Compared with the model group, that in each dose group of Codonopsis pilosula polysaccharide was decreased (P＜0.05). The results of radioimmunoassay showed that the levels of serum IL-6 and TNF-α in the model group were higher than those in the sham operation group (P＜0.05). Compared with the model group, the levels of serum IL-6 and TNF-α in each dose group of Codonopsis pilosula polysaccharide were decreased (P＜0.05). Conclusion: Codonopsis pilosula polysaccharide can inhibit excessive inflammatory response by anti-inflammatory, inhibiting thrombosis, and regulating pro-inflammatory/anti-inflammatory cytokine network, which play a therapeutic role in pulmonary embolism from multiple pathways.