Background Malignant pleural effusion is a prognostic and diagnostic sign in cancer lung .Role of tumor biomarkers in pleural fluid has been considered, but their diagnostic ability remains undetermined, therefore the aim of this current work is to evaluate the diagnostic role of both pleural fluid Angiopoietin-2 and vascular endothelial growth factor levels in malignant pleural effusions. Patients and methods: A case-control study including 56 patients diagnosed as pleural effusion of known origin. Both pleural fluid Ang-2 and VEGF levels were measured with other biochemical markers. Results: Pleural fluid VEGF could differentiate malignant exudative from benign exudative pleural effusion at a cut-off value 1590 (pg/ml),with higher Sensitivity 96.2%, Specificity 98.7% , PPV 100%,NPV 95% and Accuracy 97.8%. Additionally it has the ability to differentiate mesothelioma from other causes of malignant pleural effusion at 2225.5(pg/ml) cut off value, with Sensitivity 80%, Specificity 75%, PPV 66.7%, NPV 85.7% and Accuracy 76.9%.While Pleural fluid Ang-2, could detect malignant pleural effusion at a cut off value 15.7 ng/ml that yield lower Sensitivity 69.2%, Specificity 42.1%, PPV 62.1%, NPV 50% and Accuracy of 57.8% than that of Pleural fluid VEGF. Conclusion: Pleural fluid VEGF is a useful biomarker in diagnosing pleural effusion of malignant type, especially mesothelioma, while pleural fluid Angiopoietin-2 has a limited role in ruling out malignant pleural effusion. Key words: Malignant pleural effusion, vascular endothelial growth factor (VEGF), Angiopoietin-2(Ang-2), mesothelioma.