Pleural effusion is an accumulation of fluid in the pleural space. That occurs in patients with heart failure, pneumonias, malignancy, pulmonary embolism and tuberculosis these four causes account for more than 85%. This study was conducted on 44 patients with pleural effusions (36 patients with exudative effusions secondary to different etiologies & 8 patients in the control group with transudative effusions). All were subjected to analysis of serum and pleural fluid IL-6 & TNF-alpha. Pleural fluid IL-6 was proved significant to differentiate exudates from transudates & malignant from non-malignant pleural effusions.TNF-α was proved significant in differentiating tuberculousfrom malignant effusions.