Objective To compare the efficacy of alveolar fluid clearance(AFC) in the isolated lung and live ventilated lung models in rats.Methods Isotonic 5% Evans blue-labeled albumin solutions with different pharmacotherapeutic agents were instilled into the distal airways of the lungs of both models.AFC was estimated by Evans blue-labeled albumin at progressively increasing concentrations.Results During the first 15 min,AFC was equal in the isolated lungs and live ventilated lungs in rats.However,At 30 min after treatment,AFC in the isolated lungs was decreased to 86% of the live ventilated lungs in rats.At 60 min after treatment,AFC in the isolated lungs was 60% of the live ventilated lungs.When 10~(-4) mol/L amiloride was added into the instillation solution,a 54.3% inhibition of alveolar fluid clearance in the live ventilated lungs in rats and 50.4% inhibition in the isolated rat lungs were induced.Terbutaline increased alveolar fluid clearance 49.7% in the live ventilated lungs in rats and 44.5% in the isolated rat lungs.Conclusions Although the basal AFC in the isolated lung model is slower than that of live ventilated lung models,the effect of drug on AFC in the live ventilated and isolated rat lung models is similar.AFC can be quantified in an isolated rat lung model.It is feasible to use live ventilated or isolated model for investigations of alveolar epithelial fluid transport.The simpler isolated lung model should be useful for short-term studies of alveolar fluid clearance.