Chronic obstructive pulmonary disease (COPD) is characterized progressive airflow obstruction due to the chronic inflammation in bronchitis and the alveolar destruction. We previously showed that testosterone deficiency exacerbated porcine pancreatic elastase (PPE)-induced destruction of the alveolar structure in orchiectomy (ORX) mice, suggesting testosterone may have a suppressive effect on the progression of pulmonary emphysema. However, it remains unclear the mechanism by which testosterone suppresses the progression of pulmonary emphysema. In this study, we investigated whether testosterone supplementation attenuates pathological change (body weight loss, the infiltration of T lymphocytes into the lung, and alveolar destruction) in ORX/PPE mice. Furthermore, we examined effect of flutamide, androgen receptor (AR) inhibitor, on the enlargement of alveolar space in PPE-inhaled mice. Testosterone supplementation significantly attenuated the loss of body weight, the infiltration of T cells in bronchoalveolar lavage fluid and alveolar destruction in ORX/PPE mice. Furthermore, flutamide-treated mice show more severe emphysematous change than vehicle-treated mice. These results indicate that testosterone-androgen receptor signaling have a pivotal role in suppressing the progression of pulmonary emphysema through modulating T cell-mediated immune response.