Background: Inflammation in the adipose tissue is a key driver of obesity-related pathologies. The resolution of inflammation is actively regulated by specialized pro-resolving mediators (SPMs), such as the arachidonic acid derived eicosanoids Lipoxin A4 (LXA4) and Lipoxin B4 (LXB4). LXA4 attenuates obesity-induced adipose inflammation in mice, resulting in protection against liver and kidney disease (Börgeson et al, Cell Metabolism, 2015). The current study attempts to translate these findings from rodent to human pathophysiology. Method: White adipose tissue explants were obtained from the greater omentum of obese (BMI 35-55), non-diabetic, bariatric surgery patients (n=4). The adipose tissue was incubated ex vivo with vehicle, LXA4 (1 nM) or LXB4 (1 nM) for 6 hours at 37 degrees celsius. Supernatant cytokines were determined using ELISA, and tissue leukocytes were isolated and characterized by flow cytometry. Patients were recruited in accordance with the Helsinki Declaration; ClinicalTrials.gov #NCT02322073. ANOVA with Bonferroni correction was used to assess statistical significance. Results: In adipose tissue explants, obtained from obese patients, lipoxin treatment increased the percentage of CD206+ M2 MΦs (LXA4 +66%, LXB4 +57%), although M1 MΦs CD11c+ expression remained unaltered. Furthermore, LXA4 reduced T-cell CD69+ expression, which may reflect a less activated phenotype, although lymphocyte CD4+ and CD8+ remained unaltered. Finally, LXA4 significantly reduced adipose TNF-α levels (p<0.05), which is a key functional response in promoting metabolic health. Ongoing experiments further delineate the molecular mechanisms involved in the lipoxin-mediated attenuation of adipose inflammation. Conclusion: This “proof of concept” study indicates that lipoxins are able to attenuate adipose tissue inflammation in obese humans. Given the critical role of adipose inflammation in obesity-induced pathophysiology, our results may suggest a therapeutic potential of lipoxins in attenuating obesity-related disease.