Paleoclimatology is attached more and more importance by climate and ecological scientists. As the strengthening of the monsoon activity, the middle Holocene (6.0-5.0ka B.P.) became an important reference era of Paleoclimate Modeling Intercomparison Project (PMIP). In addition, the northeastern Qinghai-Tibetan Plateau was focused by its climatic sensibility and ecological vulnerability. In this paper, we used the data from Qinghai Lake, Zoige plateau and the source area of Yellow River to present the trends of 5000-year climate change on northeastern Qinghai-Tibetan Plateau. Then taking Zoige wetlands as an example, we reviewed studies about the impact of climate change on vegetation types, peat development and civilization evolution, and discussed the possible interaction among them. According to our analyses, the climate on the northeastern Qinghai-Tibetan Plateau was warm and humid from 5.0 to 3.0 ka B.P., with an average temperature 2℃ higher than the present. In this period, the dominant macrophanerophyte was mainly coniferous tree and the major herbage type was sedge. Moreover, thick peat accumulation was found due to the warm and humid climate. However, the climate turned into dry and cold since then to 1.0 ka B.P., with an extremely cold event around 1ka B.P.. The coniferous forest had been shrinking from highland to lowland because of fading Indian monsoon, wetlands developed very slowly and the civilization was also influenced. Meanwhile, human activities also slightly limited the development of wetlands due to the increasing population of Di-Qiang ancient people. We deduced that there existed a roughly synchronous resonance between climate change and the phenomenon of nomad migrated southward or eastward periodically. It is worth mentioning that Medieval Warm Period was observed in this era, following the prosperity of The tea-horse trade and the appearance of agricultural production by Uigur in Gansu Corridor. In recent 1000 years, due to the relatively warming climate, though not very steady, the coniferous forest and the wetland developed slightly again. In recent 100 years, the abrupt warming was introduced by increasing GHGs, the precipitation was decreased relatively. The area of Zoige wetlands decreased by a half due to drainage from 60s to the early 80s, then the shrinkage of wetlands was mainly due to climate warming, especially the abrupt warming of recent ten years. In short, the regional climate change determined vegetation types and affected the formation and development of wetlands. Climate change also impacted civilization, which altered the scope of human activity and early establishment of civilization. Meanwhile, human activities also affected the distribution and dynamics of wetlands. The interaction among climate change, wetland development and civilization course, however, depend on coupling of different factors. Furthermore, it is urgent to carry out researches about integrated adaptation and related technology on alpine's ecosystem to mitigate the climate change, as well as establishing a sustainable management system of Qinghai-Tibetan Plateau.