In conclusion, this study demonstrates that taVNS significantly improves LPS-induced depression-like behaviors by modulating peripheral pro-inflammatory cytokines (e.g., IL-1β and TNF-α) and anti-inflammatory cytokines (e.g., IL-4,IL-10) and inhibiting the activation of NF-κB signaling pathway in the prefrontal cortex. Here, NFKB1 is linked to major depressive disorder.