Acute pulmonary embolism is a common disease, which is associated with high mortality and morbidity. There is significant relationship between haptoglobin and pulmonary embolism, however, the usefulness of haptoglobin as a biomarker for the diagnosis of pulmonary embolism remains poorly defined. The aim of the present study was to investigate the change and clinical diagnostic value of haptoglobin in pulmonary embolism. A comparative proteomic analysis was used for clinical screening of serum proteins in 18 patients (9 patients with pulmonary embolism and 9 controls). ELISA was used to validate the dysregulated proteins in 48 patients (24 patients with pulmonary embolism and 24 controls). Immunohistochemical staining was performed to detect the expression of haptoglobin in pulmonary artery of both groups. The diagnostic value of the differential protein and its association with the severity of pulmonary embolism were evaluated. Eight proteins showed significant changes in serum of pulmonary embolism patients. Haptoglobin, as one of the eight differential proteins, was significantly overexpressed in the serum of pulmonary embolism patients. In accordance, the expression of haptoglobin was increased in pulmonary artery of pulmonary embolism patients. The ROC curve showed that serum haptoglobin was a specific parameter in the diagnosis of pulmonary embolism with an area under the curve of 0.764 (95% confidence interval, 0.622-0.906; P<0.01); in particular, the haptoglobin level at least 256.74mg/l was the most useful cut-off value, with the sensitivity of 62% and specificity of 83%. Increased haptoglobin level may be an acceptable diagnostic parameter for pulmonary embolism.