Postal and Appenzeller (2015) confirmed by Meta-analysis that TNF-α was significantly elevated in patients with chronic insomnia with anxiety and depression and suggested that reducing serum TNF-α levels could improve patients’ depressive symptoms. In this study, we found that IL-6 and TNF-α were significantly elevated in the brains of CUMS mice compared with Con (p < 0.05), and it was known from Figure 4B that the levels of IL-6 and TNF-α in the brains of CUMS mice were reduced to some extent after ZY-L and ZY-H interventions compared with the Mod. This evidence concerns the gene TNF and major depressive disorder.