Objective To investigate the value of tumor type M2 pyruvate kinase ( M2-PK) in the differential diagnosis of pleural effusion. Methods A total of 146 patients with pleural effusion during January 2006 to December 2008 were recruited at the department of respiratory medicine of the Shantou Affiliated Hospital and the First Affiliated Hospital of Sun Yat-sen Medical College. Pleural effusion was malignant in 72 cases ( 52 cases with lung cancer and 20 cases with metastatic lung cancer) and benign in 74 cases ( 54 cases with infective pleural effusion and 20 with transudation effusion) . The patients were divided into a malignant pleural effusion group, an infective pleural effusion group, and a transudation group.Then the infective group was further divided into subgroups of tuberculosis pleural effusion group andparapneumonic effusion group. The concentration of tumor M2-PK in pleural fluid obtained during the first thoracocentesis was measured by enzyme-linked immunosorbent assay( ELISA) . Results The concentration of tumor M2-PK was significantly higher in the malignant pleural effusion group compared with the benignpleural effusion groups ( P lt; 0. 01) . Significant differences were also found in the concentration of tumor M2-PK between malignant pleural effusion caused by lung cancer and metastatic lung cancer( P lt; 0. 05) .When the cutoff value of tumor M2-PK was set at 18. 68 U/mL, the sensitivity, specificity, and accuracy for the diagnosis of malignant pleural effusion was 87. 6% , 86. 0% , and 87. 4%, respectively. Furthermore,the detection of tumor M2-PK in combination with CEA showed better diagnostic sensitivity( 96. 0% ) ,specificity ( 85. 0% ) , and accuracy ( 91. 1% ) . Conclusions The detection of tumor M2-PK in pleural effusion is of some clinical significance in the differential diagnosis of benign and malignant pleural effusion.The detection of tumor M2-PK in combination with CEA is a good diagnostic tool with high sensitivity andspecificity.