Large mammals such as Asiatic elephant (Elephas maximus), rhino (Rhinoceros sp.), golden monkey (Rhinopithecus roxellana), gibbon (Hylobates sp.), giant panda (Ailuropoda melanoleuca), Père David's deer (Elaphurus davidianus), sika deer(Cervus nippon), and brown bear (Ursus arctos) once lived in the Dongting Lake drainage area of the middle-lower reaches of Yangtze River. However, due to climate change, geomorphological change and human disturbance, these large mammals were extirpated from thearea. After humans settled in the Dongting Lake drainage area, human activity was the major cause of the ex-tinction of local mammalian fauna, especially human hunting, habitat loss to human settlements and land reclamation. Rhino and Asiatic elephant were extirpated or emigrated from the area during the late period of the Northern Song Dynasty while Père David's deer, golden monkey, gibbon, giant panda, sika deer and brown bear became extinct in the Dongting Lake Drainage Area in the late 19th century. According to our in-vestigations during past years, such a process of species extinction is still escalating. We recorded 21 national key protected mammals in the 30 nature reserves or forest parks in the Dongting Lake drainage area. Among those species, five species are critically endangered, six species are endangered and ten species are vulner-able. Primary causes that threaten the survival of mammals are habitat loss, environmental pollution, hunting, and competition for food or habitat among wild animals. Impacts of human activities on survival of presently endangered mammalian species are much greater than ever before. These threats should be considered when reintroducing Père David's deer to the Dongting Lake region. A suitable habitat with enough foods and space and no human disturbance, a healthy founder population under close monitoring, and active conservation measures based on community co-management will be prerequisites for successful re-establishment of the extinct Père David's deer in the Dongting Lake drainage area.