Tylavlosin (TYL), a veterinary macrolide antibiotic, has been reported to have superior efficacy treating bacterial infections of the respiratory tract in swine. This study aims to characterize potential pro-resolving of tylvalosin benefits in a porcine model by elucidating its effects, in isolated neutrophils and monocyte-derived macrophages from piglets. Our findings indicate that TYL increases porcine neutrophil and macrophage apoptosis in a dose-dependent and time-dependent manners, without affecting levels of necrosis. TYL also modulates mediators of inflammation, by increasing pro-resolving lipid mediators (LXA4 and RvD1) in neutrophils and down regulating the pro- inflammatory mediators in stimulated neutrophils (LTB4) and in stimulated macrophages (CXCL8 and IL-1α). Together, these findings demonstrate that tylvalosin has immuno- modulating properties in vitro, including the induction of leukocyte apoptosis, the inhibition of pro-inflammatory cytokines and lipids mediators, and the induction of pro- resolving lipid mediators. Future studies using live piglets will help determine whether and how these effects may translate into anti-inflammatory benefits in the content of inflammatory disease within the lung.