Taken together, our results show that luteolin treatment may exert an antidepressant effect in the LPS induced depression mice by decreasing the IL-6 production by astrocytes, decreasing the serum IL-6, TNFα, and corticosterone and by increasing the levels of mature BDNF, dopamine, and noradrenaline levels in the hypothalamus. This evidence concerns the gene TNF and major depressive disorder.