Subsequently, our results showed that EZH2 silencing palliated neuroinflammation in depression rats by regulating microglia polarization as presented by the reduced iba-1 positive rate, decreased mRNA levels of M1-type markers iNOS and CD16, upregulated mRNA levels of the M2-type markers Arg-1 and CD206, declined levels of M1 pro-inflammatory factors IL-1β and TNF-α, and elevated levels of M2 anti-inflammatory factors IL-4 and IL-10. This evidence concerns the gene EZH2 and major depressive disorder.