BACKGROUND: Due to cosmic radiation bombardment and over 4 billion meteorite and micrometeoroid impacts on the airless Moon, the lunar surface is covered by a layer of fine, reactive dust. Very little is known regarding the toxicity of lunar dust on human physiology. This study assessed airborne lunar dust exposure in rats on localized pulmonary and systemic immune parameters. METHODS: Rats were exposed to 0 (air only), 20.8 (low), and 60.6 (high) mg/m RESULTS: Untreated lavage fluid was comprised primarily of pulmonary macrophages. High-dose lunar dust inhalation (60.6 mg/m CONCLUSION: Exposures to high concentrations of lunar dust resulted in persistent lung inflammation and some systemic immune dysregulation that did not subside even 13 weeks after the dust exposure. This information is beneficial in deriving an exposure limit to airborne lunar dust and for spacecraft engineers considering dust mitigation systems in lunar landers or habitats.