e23098 Background: There is no established diagnostic marker for malignant pleural mesothelioma (MPM). In particular, the differentiation from benign asbestos pleural effusion (BAPE) is challenging. Secretary leukocyte peptide inhibitor (SLPI) is an enzyme encoded by SLPI gene. SLPI gene is reported to be overexpressed in MPM cells. Methods: SLPI in pleural fluid was determined using Quantikine ELISA Human SLPI kit (R&D Systems). Results: Exploratory research revealed that SLPI value in pleural fluid of patients with MPM (n = 52) were significantly higher than those in lung cancer (LC) (n = 69) and BAPE (n = 50) ( P= 0.000). Prospective validation study included 12 pts of MPM, 24 pts of LC, 26 pts of BAPE. Median values of SLPI in MPM, LC, and BAPE were 159 .6 ng/ml, 90.5 ng/ml, and 43.2 ng/ml, respectively. SLPI value in patients with MPM were significantly higher than those in other groups ( P= 0.000). Receiver operating characteristics ROC) analysis was performed to examine the usefulness of differentiation of MPM and other diseases, and demonstrated that area under the curve (AUC) value was 0.758. With the cut of value of 88.6 ng/ml, the sensitivity was 83.3% and the specificity was 59.8%. Concerning the differentiation between MPM and BAPE, AUC value was 0.904 and with the cut of value of 81.8 ng/ml, the sensitivity was 83.3% and the specificity was 92.3%. Conclusions: Pleural fluid SLPI is a useful biomarker for the diagnosis of MPM, in particular, for the differentiation from BAPE.