Pulmonary tuberculosis (TB) is a major global health problem. Endothelin (ET)-1 is an important pro-inflammatory factor in the airways, which acts as a chemoattractant and an upregulator of other inflammatory mediators. In the present study, the association of the sputum ET-1 level with active pulmonary TB and the effectiveness of anti-TB chemotherapy was explored for the first time. A total of 56 newly diagnosed patients with active pulmonary TB, 56 age- and gender-matched TB-free controls, and 43 subjects with latent TB were recruited to the study. Patients in the active TB group received standard anti-TB chemotherapy. Sputum samples were collected from all study subjects at baseline (day 0) and on days 1, 2, 4, 6, 10 and 14 of treatment for the active TB group and the ET-1 level was determined by enzyme-linked immunosorbent assay. The sputum ET-1 level in the active TB group was significantly higher than those in the latent TB and the non-TB groups at baseline. Following adjustment for confounders such as age, gender, severity of clinical presentation, plasma ET-1 level and comorbidities that might affect the sputum ET-1 level, multivariate logistic regression analysis revealed that sputum ET-1 level was an independent indicator for active pulmonary TB. In the active TB group during anti-TB chemotherapy, decrements in the sputum ET-1 level were in significant correlation with decrements in the number of colony-forming units and increments in the time to positivity in a Mycobacteria Growth Indicator Tube assay. In conclusion, this study indicates that an elevated sputum ET-1 level is an independent indicator of active pulmonary TB and suggests that decrements in the sputum ET-1 level could reflect the effectiveness of anti-TB chemotherapy.