Background: Tuberculous pleurisy and malignancy are two of the most common causes of pleural effusion. IL-33 is expressed in the epithelial lining and endothelial cells and is released after cell damage; it is proposed to have an essential role in sensing damage in various infectious and inflammatory diseases. This work aimed to determine the diagnostic role of IL-33 in pleural effusions. Methods: One hundred seventeen patients with pleural effusions of different etiologies had a quantitative measurement of IL-33 in their pleural effusion and serum samples by ELISA technique. Results: The concentrations of IL-33 (mean ± SD) in tuberculous pleural effusion (TPE) group (22.5 ± 0.90 ng/l) were significantly higher than that of malignant pleural effusion (MPE) group (14.6 ± 2.35 ng/l; P < 0.001). There is no significant difference between the serum levels of IL-33 in (TPE) group and (MPE) group (P > 0.05). The concentrations of IL-33 in the pleural effusions were significantly correlated to that of the serum concentrations in each group (TPE: r = 0.848, P = < 0.001; MPE: r = 0.881, < 0.001) and pleural ADA in patients with tuberculous pleural effusions, (r = 0.38, P < 0.001). The cut-off value of pleural IL33 for (TPE) was 19.16 ng/l, with a sensitivity of 91.7%, a specificity of 96.4%. The cutoff point of a pleural/ serum IL-33 ratio for the diagnosis of TPE was > 1.4 with a sensitivity of 91.7% and specificity of 100% while for the determination of (MPE) was < 0.9 with a sensitivity of 83.3% and specificity of 96.4%. Conclusion: IL-33 level may serve as a novel biomarker to differentiate pleural effusions, especially tuberculous from malignant effusions.