Aims: In the lung, beta-2-adrenergic receptor (b2AR) stimulation increases alveolar reabsorption and tightens the alveolar barrier thus protecting from edema formation. Hypoxia causes alveolar edema by inhibition of alveolar reabsorption and increased permeability. It also impairs b2AR signalling in vitro in alveolar epithelium. Therefore we tested how prolonged in- vivo treatment with terbutaline affects b2AR signalling and alveolar reabsorption in normoxic and hypoxic rats. Methods: Terbutaline was applied 2x daily i.p. (5mg/kg/d) to rats exposed to normoxia and hypoxia (8% O2) for four days. b2AR signalling was measured on freshly isolated ATII cells. In separate experiments, alveolar reabsorption was measured after fluid instillation. Results: Four days of in-vivo treatment with hypoxia and terbutaline decreased basal cAMP production, which was restored by PTX application indicating that Gi/o proteins were involved. cAMP production after terbutaline stimulation was decreased in ATII cells from hypoxic and terbutaline treated rats, which was not restored by PTX. Adenylyl cyclase activity measured as forskolin-stimulated cAMP production was not changed in ATII cells from treated rats. b2AR density in ATII cells was decreased by 4d terbutaline-treatment in normoxia and hypoxia, but was increased by hypoxia alone. Western blot analysis showed that Gs and Gi proteins were not changed by the different treatments. Hypoxia alone and terbutaline treatment increased GRK2 protein expression. Exposure to hypoxia for 4 days decreased alveolar fluid reabsorption significantly. However, in terbutaline-treated, hypoxic rats alveolar reabsorption was increased reaching normoxic control values. Conclusion: These results indicate that despite impairment of b2AR signalling by terbutaline treatment and exposure to hypoxia, four days of b2AR- stimulation blunts the inhibition of alveolar reabsorption caused by hypoxia.