The present results showed that IL-1β, IL-6, and NF-κB/NLRP3 inflammatory signaling pathway proteins increased in the mPFC in ICV-STZ rats when they exhibited depression- and anxiety-like behaviors, suggesting that ICV-STZ-induced neuroinflammation might be a potential pathological mechanism by which these abnormalities occurred. Here, NLRP3 is linked to major depressive disorder.