Neovestitol is considered one of the main bioactive components of Brazilian red propolis. Neovestitol's antimicrobial and antioxidant effects have already been demonstrated. Here, neovestitol immune modulatory effects were investigated on LPS activated macrophages. RAW264.7 murine macrophages activated with LPS were treated with neovestitol and NO production, cell viability and cytokines profile were determined. Activation of inflammatory signaling pathways and macrophage polarization were determined by RT-qPCR and Western blot. Neovestitol at 0.22 mu M inhibited NO production by 60% without affecting cell viability and reduced GM-CSF, IFN-gamma, IL-1 beta, IL-4, TNF-alpha and IL-6 levels, whereas increased IL-10 production. These cytokines profile changes were associated with the downregulation of transcription of genes involved in nitric oxide production, NF-KB, IL-1 beta, and TNF-alpha signaling pathways. NF-KB and MAPK signaling pathways inhibition and decreased levels of TIRAP were further confirmed by Western blot. Neovestitol, as a nutraceutical, is a potential candidate to modulate chronic inflammation in humans Ver menos