Micro- and nanoplastics (MNPs) are one of the most widespread pollutants of our time. They can be manufactured in specific sizes for a specific purpose or be released into the environment through the degradation of plastic products. Humans are generally exposed to MNPs via two main routes: food ingestion or inhalation of air. In the latter case, it has already been reported that airborne particles can enter and accumulate in the lower respiratory tract, leading to occupational diseases. This study aims to assess the impact of 274 nm europium-doped polystyrene (PS-Eu) particles on the integrity and functionality of the lung barrier, especially in terms of surfactant production. The presented results were produced both on A549 cells grown in “standard” submerged (Sub) conditions as well as by performing the assays in Air-liquid interface conditions (ALI) using transwells which resemble more closely the real-life settings.