This paper contains the main characteristics of the settlements in the part of Euro region Danube XXI (East Serbia). The changes in the settlements of this region after the World War Two were very intensive and they have been happened by the industrialization and urbanization influence. One of the results of these processes was very expressive problem of depopulation especially in this region of the Republic. The changes in the surrounding settlements of the cities were weekly. Generally, settlements and centers are on the lower development level than on the other territory of Republic. Functional and territorial organization of those settlements, beside their development, is an important factor for realization of integration processes of this region in the wider surroundings.