Taken together, these findings indicate that FA and ACT maintain the balance of microglial M1/M2 polarization in a collaborative manner to attenuate prefrontal neuroimmune inflammatory responses in CUMS‐induced depression by suppressing RORγt/IL‐17AR signaling and promoting the Nrf2/TREM2/DAP12/Arg‐1 pathway. This evidence concerns the gene TYROBP and major depressive disorder.