PLGA (50:50) nanoparticles were prepared to sustain the release of Ethionamide in order to decrease the dose and dosing frequency. It further modified in the form of dry powder inhaler to make suitable for pulmonary administration and increase drug residency in lungs. Ethionamide loaded PLGA nanoparticles were prepared by solvent evaporation method. Freeze dried nanoparticles and anhydrous inhalable grade lactose were mixed manually using geometrical dilution process to modify the nanoparticles in the form of dry powder inhaler. Animal study was conducted to correlate between in-vivo and in-vitro. PLGA nanoparticles showed initial burst release followed by zero order release up to 95.17 ± 3.59% in 24 h. Aerodynamic particle size of optimized dry powder inhaler was found as 1.79 μm. There was no significant aggregation of dry powder inhaler during 6 months of stability study. Area under the concentration-time curve from 0 h to infinity (AUC0−∞) signifies the prolong residency of ETH in body compartment, revealed from animal study. PLGA 50:50 coated nanoparticles released Ethionamide for the period of 24 h in simulated lungs fluid. Correlation between in-vitro dissolution and in-vivo study was established after performing animal study. Prepared dry powder inhaler maintained Ethionamide concentration above minimum inhibitory concentration for more than 12 h after single dose administration.