Scope Adipose tissue is infiltrated by an increasing number of macrophages during the development of obesity. These immune cells are suspected to be a major source of TNF-a that interferes with adipocyte function. Because lycopene possesses anti-inflammatory properties, we hypothesize that lycopene could reduce the production of TNF-a by macrophages and thus interfere in the cross-talk between macrophages and adipocytes. Methods and results We demonstrated that physiological concentrations of lycopene were able to attenuate the lipopolysaccharide (LPS)-mediated induction of TNF-a in RAW 264.7 macrophages, at both the mRNA and protein levels. The molecular mechanism was studied. It appeared that the LPS-activation of both JNK and NF-?B signaling pathways was modulated by lycopene. The anti-inflammatory effects of lycopene on macrophages were accompanied by a decrease in LPS-stimulated macrophage migration in the presence of lycopene. Furthermore, lycopene decreased macrophage conditioned medium-induced proinflammatory cytokine, acute phase protein, and chemokine mRNA expression in 3T3-L1 adipocytes. Conclusion These data indicate that lycopene displayed an anti-inflammatory effect on macrophages that beneficially impacted adipocyte function. Thus, these results suggest that lycopene could block the vicious cycle that occurs between adipocytes and macrophages in adipose tissue during obesity.