Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) ; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) ; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ; Processo FAPESP: 09/54190-0 ; Processo FAPESP: 10/18968-3 ; Tea tree oil (TTO) is an essential oil with anti-inflammatory properties, steam distilled from the plant Melaleuca alternifolia. We investigated the immunomodulatory properties of TTO and its components (terpinen-4-ol and alpha-terpineol) using lipopolysaccharide (LPS)-stimulated macrophages.The ability of TTO, terpinen-4-ol and alpha-terpineol to modulate the macrophage response to bacterial LPS stimulation was assessed by ELISA for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6 and IL-10 cytokine production and by western blotting for the activation of nuclear factor kappa B (NF-kappa B) and p38 mitogen-activated protein kinase (MAPK) signaling, which are associated with the expression of pro-inflammatory cytokines. We used a human monocytic cell line (U937) differentiated into macrophages.LPS induced the production of all cytokines, and TTO and its components significantly reduced the production of IL-1 beta, IL-6 and IL-10. The production of TNF-alpha was not affected by either TTO or its major components. The modulation of cytokine production was not mediated by changes in NF-kappa B or p38 MAPK activation.TTO, terpinen-4-ol and alpha-terpineol can suppress the production of inflammatory mediators in LPS-stimulated human macrophages; this inhibition was mediated by interfering with the NF-kB, p38 or ERK MAPK pathways.