To assess the feasibility of selective delivery of chemotherapy in lung using a double balloon occlusion catheter in subsegmental pulmonary arteries (PA) to increase tissue drug concentrations relative to intravenous (IV) administration. Four adult swine were used in this IACUC approved protocol. Via transjugular access, a 6F double balloon-occlusion catheter (RenovoRx Rc-120, Los Altos, CA) was used to isolate a subsegmental branch of the left lower lobe PA in three swine. 5000 IU heparin was given IV. Gemcitabine at 1g/m2 was administered under flow isolation over 20 minutes using an infusion pump (150 max PSI). Gemcitabine at 1g/m2 was administered IV over 20 minutes in a control animal. Peripheral blood was collected during infusion to test systemic drug concentrations. After drug infusion, 6cc methylene blue was infused via the same technique to stain perfused lung tissue. Animals were sacrificed and stained lung was harvested for gemcitabine concentrations. Selective delivery of gemcitabine to subsegmental PA under double balloon occlusion was feasible in all animals. No PA injury occurred and there were no arrythmias. By inspection, no pulmonary hemorrhage or overt injury was seen. Dense methylene blue staining was observed in the parenchyma of animals treated with selective PA delivery up to 3cm around the isolated segment, whereas no discernible blue stain was seen in the animal with IV delivery. Tissue analysis revealed approximately 100x greater tissue gemcitabine levels in animals treated via PA compared to IV (1,272.83 vs. 13.40 mcg/g tissue, T-test, p<0.02). Systemic drug concentrations varied widely from 10%-100% of IV dosing. Selective delivery of chemotherapy to lung via double balloon-occlusion isolation of pulmonary arteries is feasible and led to significantly greater tissue drug concentrations compared with IV administration. Further investigation will investigate the variability in systemic levels to characterize the pharmacokinetic profile for optimized delivery. If successful, this strategy may be promising for treatment of lung cancers not amenable to surgical or ablative techniques.