Objective To investigate the correlation of plasma periostin (POSTN), endothelin-1 (ET-1), and N-terminal natriuretic peptide precursor (NT-proBNP) with coagulation function and hemorheological indexes in patients with chronic pulmonary heart disease (CPHD), and provide relevant basis for clinical diagnosis and treatment. Methods The clinical data of 75 CPHD patients admitted to DujiangyanTraditional Chinese Medicine Hospital from January 2020 to September 2021 were retrospectively analyzed, and they were divided into the group A (35 patients with acute exacerbation) and the group B (40 patients with acute exacerbation of CPHD) according to the degree of disease progression, and the clinical data of 50 healthy people who underwent physical examination during the same period were retrospectively analyzed, and which was used as the healthy physical examination group. The plasma POSTN, ET-1, NT-proBNP levels, arterial blood partial pressure of carbon dioxide (PaCO2), arterial blood partial pressure of oxygen (PaO2), right ventricular ejection fraction (RVEF), coagulation function and hemorheology indexes among the three groups of subjects were compared , and the correlation of plasma POSTN, ET-1, NTproBNP levels with coagulation function and hemorheological indexes were analyzed. Results The plasma POSTN, ET-1, NT-proBNP and PaCO2 levels of patients in the group A and the group B were higher than those in the healthy physical examination group, and the group B was higher than the group A; the levels of PaO2 and RVEF were lower than those in the healthy physical examination group, and the group B was lower than the group A; prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of patients in the group A and the group B were longer than those in the healthy physical examination group, and the group B was longer than the group A; whole blood high shear viscosity, whole blood low shear viscosity, hematocrit (HCT), plasma viscosity and erythrocyte sedimentation rate (ESR) were higher than thoes in the healthy physical examination group, and those in the group B were higher than thoes in the group A; plasma POSTN, ET-1, NT-proBNP levels were positively correlated with PT, APTT, TT, HCT, whole blood high shear viscosity, whole blood low shear viscosity, plasma viscosity, ESR, PaCO2, and negatively correlated with PaO2 and RVEF (all P<0.05). Conclusion Plasma POSTN, ET-1, NT-proBNP levels can gradually increase with the aggravation of CPHD patients, and wihch are correlation with coagulation function, hemorheology and other indicators. The detection of plasma POSTN, ET-1 and NT-proBNP has certain reference value for predicting the severity of CPHD patients and for early diagnosis and treatment.