This paper describes the course of migration and expansion of small mammals in the Makalu Barun region influenced by the orogenetic uplift of the East Nepal Himalaya and climatically conditioned changes in the extent of morphogenetic zones from the Upper Pleistocene up to the present. The results of zoological and parasitological research are compounded with the knowledge of the dynamic development of landforms, which testifies to significant changes in the high-mountain environment during the Quaternary. The migration of Palearctic species of small mammals across the gradually emerging orographical barrier during the orogenesis of the High Himalaya was completely interrupted by the glaciation in the Upper Pleistocene. This extensive glaciation also excluded occurrence and survival of small mammals in the high-mountain valleys of the Makalu Barun region. Migration routes and the extension of the territory of small mammals remained open only in the periglacial zone of the Arun and Barun Khola valleys. Following the interstadial period of warmer and humid climate conditions were changed by the Late Glacial Maximum when small mammals were again pushed away from heavily glaciated valleys to the lower altitude periglacial zone. During the Holocene interglacial, the occurrence of fauna and flora in the high-mountain valleys depended on repeated spatial changes of periglacial and glacial morphoclimatic zones. Current biogeographical hazards are accentuated due to the rapid retreat of glaciers, the expansion of the periglacial morphoclimatic zone and the increased human impact in the High Himalaya.