Backround and Purpose. Proton pump inhibitors (PPI) are the most commonly used medication in the world. They are prescribed as an effective treatment choice for gastrointestinal system diseases linked to hyperacidity, especially. Many publications in recent times have reported significant side effects. However, there are insufficient studies about the topic of the mechanism for these side effects. Experimental Approach. Rats were divided into 3 groups of control, a group administered H2 receptor blockers and a group administered PPI (n: 8). Medications were administered for 30 days intraperitoneal. After 30 days, rats were euthanized and lung tissue was obtained. Lung were stained for immunohistochemical Catalase, Superoxide Dismutase, Glutation Peroxidase, Myeloperoxidase and toluidine blue and investigated with a light microscope. Transmission Electron Microscopy (TEM) was used to investigate lung tissues and neutrophil leukocytes. Additionally, lung tissue had biochemical H2O2 levels researched. Key Results. H2O2 amounts, produced by lysosomes with important duties for neutrophil functions in lung tissues, were found to be statistically significantly reduced in the group administered PPI. Results of investigations of preparates obtained with immunohistochemical staining observed increases in antioxidant amounts in the PPI group. Investigation with TEM identified more inflammation findings in the lung tissue from the group administered PPI compared to the control group and the group administered H2 receptors. Conclusion and Implications. In conclusion, we identified long-term PPI use disrupts neutrophil leukocyte functions in lung. All clinicians should be much more careful about PPI use.