To investigate the concentrations and clinical significance of interleukin (IL)-20 and IL-22 in pleural effusion with various etiologies.Pleural effusion (PE) and corresponding serum samples were obtained from 88 patients from Wuhan Tuberculosis Prevention and Control Institute from June 2011 to June 2013. There were 27 cases with malignant pleural effusion, 24 with tuberculous pleural effusion, 17 with bacterial pleural effusion and 20 with transudativeeffusion. The pleural and serum levels of IL-20 and IL-22 were determined by sandwich enzyme-linked immunosorbent assays (ELISA).(1) Except for transudativeeffusion, the concentration of IL-20 in malignant pleural effusion (36.8±5.1) ng/L, tuberculous pleural effusion (34.8±6) ng/L, bacterial pleural effusion (41.7±20.2) ng/L, were significantly higher than that of the corresponding serum concentration (29.7±5.97) ng/L, (27.3 ±6.7) ng/L, (25.6±4.7) ng/L (t=5.044, 3.804, 3.452, P0.05). The concentration of IL-22 (median, quartiles) in tuberculouseffusion was 146.1 (39.8) ng/L and bacterial effusion 59.6 (484.3) ng/L was significantly higher than those in the corresponding serum concentrations 18.7 (9.8) ng/L, 15.7 (17.2) ng/L (Z value respectively -3.971, -3.290, P<0.05). The concentration of IL-22 in tuberculous pleural effusion, bacterial pleural effusion, transudative pleural effusion was significant higher than those in malignant pleural effusion respectively (all P<0.001). (2)The concentrations of IL-22 in malignant pleural effusion was correlated positively with those in serum (r=0.729, P<0.001). (3) With a cut-off value of 19.7 ng/L, pleural IL-22 exhibited a high sensitivity and specificity of 95.1% (39/41) and 88.9%(24/27) respectively, when used for distinguishing infectious pleural effusion (including tuberculous and bacterial effusion) from malignant pleural effusion (P<0.001).Higher levels of IL-22 in tuberculous and bacterial pleural effusion were found when compared with corresponding serum levels and might be involved in the pathogenesis of infectious pleural effusion. Pleural IL-22 measurement provided reliable diagnostic efficiency for distinguishing infectious from malignant pleural effusion.