Background: Chlorine (Cl2)-induced lung injury is a serious public health threat that may result from industrial and household accidents. Post-Cl2 administration of aerosolized ascorbate in rodents decreased lung injury and mortality. However, the extent to which aerosolized ascorbate augments depleted ascorbate stores in distal lung compartments has not been assessed. Methods: We exposed rats to Cl2 (300 ppm for 30min) and returned them to room air. Within 15-30min postexposure, rats breathed aerosolized ascorbate and desferal or vehicle (mean particle size 3.3μm) through a nose-only exposure system for 60min and were euthanized. We measured the concentrations of reduced ascorbate in the bronchoalveolar lavage (BAL), plasma, and lung tissues with high-pressure liquid chromatography, protein plasma concentration in the BAL, and the volume of the epithelia lining fluid (ELF). Results: Cl2-exposed rats that breathed aerosolized vehicle had lower values of ascorbate in their BAL, ELF, and lung tissues compared to air-breathing rats. Delivery of aerosolized ascorbate increased reduced ascorbate in BAL, ELF, lung tissues, and plasma of both Cl2 and air-exposed rats without causing lung injury. Based on mean diameter of aerosolized particles and airway sizes we calculated that approximately 5% and 1% of inhaled ascorbate was deposited in distal lung regions of air and Cl 2-exposed rats, respectively. Significantly higher ascorbate levels were present in the BAL of Cl2-exposed rats when aerosol delivery was initiated 1h post-Cl2. Conclusions: Aerosol administration is an effective, safe, and noninvasive method for the delivery of low molecular weight antioxidants to the lungs of Cl2-exposed individuals for the purpose of decreasing morbidity and mortality. Delivery is most effective when initiated 1h postexposure when the effects of Cl2 on minute ventilation subside. © Copyright 2012, Mary Ann Liebert, Inc. 2012.