An effect of the Vitamin A metabolite all-trans-retinoic acid (ATRA) on body weight regulation and adiposity has been described, but little is known about its impact on obesity-associated inflammation. Our objective was to evaluate the overall impact of this metabolite on inflammatory response in human and mouse adipocytes, using high-throughput methods, and to confirm its effects in a mouse model. ATRA (2 μM for 24 h) down-regulated the mRNA expression of 17 chemokines in human adipocytes, and limited macrophage migration in a TNFα-conditioned 3 T3-L1 adipocyte medium (73.7%, P<.05). These effects were confirmed in mice (n=6–9 per group) subjected to oral gavage of ATRA (5 mg/kg of body weight) and subsequently injected intraperitoneally with lipopolysaccharide. In this model, both systemic and adipose levels of inflammatory markers were reduced. The antiinflammatory effect of ATRA was associated with a reduction in the phosphorylation levels of IκB and p65 (~50%, P<.05), two subunits of the NF-κB pathway, probably mediated by PGC1α, in 3 T3-L1 adipocytes. Taken together, these results show a significant overall antiinflammatory effect of ATRA on proinflammatory cytokine and chemokine production in adipocyte and adipose tissue and suggest that ATRA supplementation may represent a strategy of preventive nutrition to fight against obesity and its complications.