Lymphangioleiomyomatosis (LAM) is a systemic interstitial lung disease mainly affecting women of childbearing age. It?s characterized by cystic lung destruction, lung remodeling and progressive respiratory failure. Krebs von den lungen-6 (KL6) is mainly produced by fibrotic damaged or regenerating alveolar type II pneumocytes, while interleukin-6 (IL6) is a pro-inflammatory marker involved in the pathogenesis of various chronic diseases. Eight LAM patients (mean age 43 y/o; 8 females) and ten healthy controls (HC) (mean age 43.7 y/o; 6 females) were enrolled in the study. In both populations KL6 and IL6 have been dosed. All LAM patients had higher IL6 and KL6 concentrations than HC. ROC curve analysis allowed to distinguish LAM and HC according to IL6 cutoff value of 21.8pg/mL (p=0.0209; sensitivity 70% and specificity 75%). KL6 cutoff value of 247U/mL allowed to discriminate LAM and HC (p=0.0022; sensitivity 80% and specificity 87.5%). To improve the diagnostic accuracy, logistic regression analysis was performed considering LAM condition as a dependent variable versus HC. Serum KL6 and IL6 were tested as independent variables and the model showed AUC 91.2% (p=0.0034; negative predictive value 90.9% and positive predictive value 100 %). Our findings demonstrated the balance between inflammation and fibrosis in LAM patients according to IL6 and KL6 concentrations. This result shines a spotlight on the presence of a greater inflammatory and fibrotic state in patients than HC. Our serum biomarkers? panel (KL6 + IL6) could be a potential diagnostic tool to evaluate diagnosis and prognosis of LAM patients, highlighting the need to further evaluate them in a larger and multicenter cohort.