Abstract Body: Neutrophils are major contributors to inflammatory reactions. Neutrophil-platelet interaction is crucial in the development of both cardiac and blood diseases. Neutrophils and platelets interact through adhesion molecules such as L-selectin (CD62L), contributing to thrombosis and inflammation. This interaction plays a key role in cardiovascular diseases like myocardial infarction and atherosclerosis, as well as thrombo-inflammatory diseases. Neutrophils can modulate the function of platelets through secretory molecules leading to a prolonged chronic state of low-grade inflammation. During the course of low-grade inflammation leukocytes infiltrate the vascular endothelium to migrate to the inflamed tissue, platelets can modulate the function of neutrophils by facilitating their migration through disrupted endothelial of blood vessels, this interaction involves the leukocyte adhesion cascade which is critical in the process of trans-endothelial migration, however, there is a gap in our knowledge on how neutrophiles work together with other cells during low-grade inflammation. The balance between the inflammatory response and resolution of neutrophils is crucial to achieve homeostasis in the blood vessels, we hypothesize that neutrophiles use PEX5 peroxisomal transport machinery as a regulatory mechanism to control the inflammatory response. In the present study we used PEX5 knock out mice to examine the response of different neutrophil subsets to LPS and 4-PBA in an in vitro culture model. Purified mouse neutrophils were cultured overnight then cells were harvested and followed by neutrophiles-platelets assay. Our Results showed that the genetic deletion of PEX5 caused neutrophil exhaustion which led to more activation of platelets. By comparing levels of CD11b and CD38 in Pex5+/+ neutrophils and Pex5-/- neutrophils, we found that their levels were higher in Pex5-/- neutrophils, also we found that the level of CD41 was subsequently increased in the Pex5-/- aggregated cells. Taken together, our data reveal that PEX5 may have a potential in the mechanism of regulating the interaction between neutrophiles and platelets in low grade inflammation driven cardiac disease including atherosclerosis.