Serum amyloid A (SAA) is an acute-phase protein that has been recognized as a diagnostic biomarker for several diseases. However, the functional studies about the effects of SAA on microglial activation seem controversial. Here, we discovered that SAA induces microglial cells polarize to a pro-resolving M2 phenotype by promoting the stability of the transcription factor Nrf2, which specifically regulates microglia towards a pro-resolving phenotype via metabolic reprogramming. Moreover, we identified that the AMPK/mTOR signaling pathway is involved in SAA-induced Nrf2 upregulation. Additionally, SAA protects cultured neuronal cells from MPP