Objective To study the differential diagnosis value of combined measurement of VEGF,CEA and telomerase between benign and malignant pleural effusions . Methods Seventy patients with pleural effusions were observed, including 34 cases of malignant pleural effusions and 36 cases of benign effusions. VEGF and CEA levels in pleural effusion were detected by ELISA.Telomerase activity was tested by PCR-ELISA.Results The expresions of VEGF, CEA and telomerase in the group of patients with malignant pleural effusion were significantly higher than those in the benign group (P<0.05). In single-item detection, the sensitivity and positive predictive values of VEGF were highest (73.53%,83.33%). The specificity of CEA was highest(88.88%). In combined examination, the sensitivity of VEGF+CEA was highest, and the specificity level of CEA+telomerase was lower than that of VEGF+CEA and VEGF+telomerase. Conclusions VEGF, CEA, and telomerase hare high value in the differential diagnosis of benign and malignant pleural effusions. Combined examination can improve the diagnostic sensitivity.