Neutrophil transmigration through venular walls is an important physiological reaction to inflammatory insults. This response normally occurs in vivo in a luminal-to-abluminal direction, however neutrophil reverse transendothelial migration (rTEM) has been observed in an in vitro flow model1. Furthermore, we recently reported on the occurrence of directionally disrupted modes of neutrophil TEM in an in vivo mouse model of ischemia-reperfusion (I-R) injury2; namely “hesitant” TEM (characterised by oscillatory movements within the endothelial cell junction followed by complete transmigration) and reverse TEM (migration in an abluminal-to-luminal direction resulting in return of the neutrophil to the circulation). Of importance, the latter was causally linked with the appearance of a phenotypically distinct and pathogenic subset of neutrophils found within the lung vasculature2. The present study further characterises the profile and prevalence of these rare and disrupted TEM phenomena in response to a range of inflammatory agents. Neutrophil TEM was induced in the cremaster muscle microcirculation of LysM-EGFP+/- mice through local application of multiple inflammatory stimuli. Dynamics of neutrophil TEM was subsequently measured under ketamine/xylazine anaesthesia by 4D confocal intravital microscopy as previously detailed 2. Neutrophils in the blood, pulmonary vasculature and lung tissue were quantified and phenotypically analysed by flow cytometry. TEM induced by LPS and leukotriene B4 involved a high frequency of rTEM (~10-25% of all TEM events quantified), whereas TNF and HMGB1 caused low levels of rTEM (~0-2%), but were associated with significant levels of ‘hesitant’ TEM (~11-21%). In contrast, a relatively low percentage of disrupted TEM events was observed in KC and IL1-β-stimulated tissues. In all the models investigated, the frequency of rTEM was associated with the occurrence of lung inflammation alongside a sub-set of ICAM-1+ve neutrophils in the pulmonary vasculature. Our findings demonstrate that inflammatory stimuli can cause distinct neutrophil TEM dynamics, which specifically contribute to the pathogenic outcome of these reactions at sites distant from the inflammatory insult.