Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients ’ outcomes . This might be because dependent lung areas cannot be reached by conventional aerosols . Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem . After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen . Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen . Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured . The ibuprofen concentration was equally distributed to the dependent parts of the right lungs . Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane . A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics . F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics.