Depression is a very serious mental illness that affects nearly 20 percent of the US population and results in enormous personal suffering and socioeconomic burden. A major contributing factor to depression is uncontrollable stress, which can precipitate or exacerbate depression. Stress-induced reduction of hippocampal neurogenesis has been extensively investigated, based on the idea that the therapeutic effects of antidepressants involve a reversal of the stress-induced hippocampal impairment. However, the mechanisms underlying the anti-neurogenic and behavioral actions of stress to pathophysiology of depression remain ill defined. One possibility is interleukin (IL)-1β, which is a pro-inflammatory cytokine that has been implicated as a mediator of stress and a causative factor in emotional disorders, including depression and anxiety. In chapter 2, I demonstrate that IL-1β underlies the anti-neurogenic effects of stress. Both acute and chronic stress suppressed hippocampal neurogenesis, of which the down-regulation was blocked by pre-administration of IL-1 receptor antagonist (Ra). The role of IL-1β in the anti-neurogenic actions of acute and chronic stress was further confirmed in mice with a null mutation of the only effective IL-1β receptor, IL-1RI. In chapter 3, I show a role of IL-1β in the anhedonic effects of chronic unpredictable stress (CUS). The pharmacological and genetic inactivation of IL-1RI blocked the anhedonic behavior resulting from CUS. Furthermore, I charaterized the role of IL-1β in anxiety and fear models with IL-1RI null mice, which revealed that the IL-1β/IL-1RI system may directly influence anxiety and fear memory formation. In chapter 4, I explore the mechanisms underlying the anti-proliferative actions of IL-1β using cultured rat adult hippocampal progenitors. I found that that IL-1β and IL-1Ra act on cell proliferation via the IL-1R1 expressed on the neural progenitors. The anti-proliferative action of IL-1β occurs through regulating the cell cycle, in particular, the expression of cyclin D1 and through activation of the nuclear factor-κB pathway in adult hippocampal progenitors. Taken together, my findings demonstrate that IL-1β is a key mediator of stress on adult hippocampal neurogenesis and depression-related behaviors.