The results showed that oral gavage of sake in higher doses decreased anxiety-like and depression-like behaviors (p = 0.000), increased the concentrations of BDNF (p = 0.000) and FRAP (p = 0.000), and reduced the concentration of MDA (p = 0.000) and the expressions of IL-1β (p = 0.000), TNF-α (p = 0.000), and IL-6 (p = 0.000). This evidence concerns the gene IL6 and major depressive disorder.