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Rodents are the major remaining mammals in many terrestrial ecosystems after the historical loss of megafauna and large-bodied taxa. Niviventer confucianus is a dominant habitat generalist in natural forests in most of China. It is also recorded as an important vector of diverse zoonotic diseases. Here, three mitochondrial and one nuclear DNA fragments were sequenced from samples covering most of the species range to study intraspecific genetic diversification and demographic history. Molecular voucher specimens of N. confucianus revealed that its assumed distribution range has been overestimated because of the hitherto unrecognized separation from parapatric species. Phylogenetic inferences recognized three geographically delimited intraspecific lineages that diverged at approximately 1.28 and 0.68 Mya. Hengduan Mountains, the east margin of Qinghai Tibetan Plateau, and the mountains surrounding Sichuan Basin were recognized as the major geographical barriers. Demographic analysis revealed dramatic population growth in southwest, central, and northern China in the late Pleistocene, but only slight growth in Yunnan/Tibet. The population boom apparently coincided with the reduction of predation and competition from the loss of megafauna in the late Pleistocene. Distributional ranges were inferred to be fairly stable through the late Quaternary glacial-interglacial climatic oscillations, possibly enabled by the species' seed hoarding behavior and wide climatic tolerance. The demographic history of N. confucianus suggests that these rodents directly profited from the loss of megafauna, while their most recent increases potentially led to the proliferation of zoonotic disease by this species.