Remodeling processes during chronic lung disease are mediated by chemical, biomechanical, and neuro-endocrine mechanisms. We studied the effect of pharmacological blockade of angiotensin II type 1 (AT1) receptors on pulmonary and extrapulmonary manifestations of lung emphysema in mice. Emphysema was induced by repetitive (5-fold) weekly intratracheal administrations of porcine pancreatic elastase. This substantially increased alveolar diameter, lung volume, and static compliance of the lung. Maximal exercise capacity was reduced, indicating impaired gas exchange, while urine catecholamine excretion increased, indicating generalized sympathetic activation. Oral treatment of emphysema mice with the AT1 receptor antagonist irbesartan (50 mg/kg BW and day) for 8 wks, starting 3 wks after the last elastase administration, resulted in a significant reduction of alveolar diameters and static compliance of the lungs, compared with untreated emphysema mice. Thus, the structural alterations associated with lung emphysema were ameliorated, although not completely normalized. Furthermore, exercise capacity was maintained and urine catecholamine excretion reduced. Our results indicate that angiotensin II is a critical mediator of structural remodelling processes in the lung during chronic pulmonary disease and that pharmacological blockade of its action may exert beneficial effects.