Depression is one of the most common psychiatric disorders. Despite the prevalence and serious effects of depression, pathological studies of depression are still preliminary. The main reason for this is limited access to valid animal models. Using animal models, the underlying molecular changes and causal relationship between environmental or genetic changes and depression can be studied, which provides a better insight into the pathology of depression. The role of stress as a key factor in the etiology of depression is emphasized. Because of the importance of stress in creating depression disorder in this study, animal models of stress-based depression have been investigated. Animal models of stress-based depression are:1- learned helplessness (LH) model 2- Models based on early-life stress 3- chronic mild stress (CMS) model 4- Social defeat stress model. Studies show that exposure to early life stress can continuously alter DNA methylation in the brain of adult mice or rodents. In this regard, we can mention the role of methylation of the Nr3c1 gene in parts of the hippocampus of the brain, indicating that epigenetic changes may play a role in depressive-like behavior. Also, an unpredictable chronic mild stress model in rodents shows that significantly reduced diffusion of astrocyte cell gap and abnormal ultrastructure gap junction in the prefrontal cortex (PFC) and low levels of adenosine triphosphate (ATP) in the mouse brain, are the cause of depressive-like behavior.