This article describes the main trends in the changes to the system of rural settlements in Lithuania and determines the regional peculiarities of these changes. The analysis was carried out using data collected during the censuses of 2001 and 2011, and information that was gathered during field trips to rural settlements across the country in 2013 and 2014. Our analysis showed that the population decreased in the majority of settlements independently of their size. However, distinct regional differences can be identified and these were especially evident when comparing the data collected from the rural settlements located close to the capital city (Vilnius) or regional centres (Kaunas, Klaipėda, Šiauliai, Panevėžys and Alytus) with the data collected from the peripheral areas located further from cities or roads of regional importance. The survey showed that the north-eastern and southern parts of Lithuania are depopulated most, whereas in the western part of the country the number of residents was stable until 2000, and only in the 21st century did it start to decrease due to the increasing emigration rates. Also, the analysis of the structure of settlements allowed us to point out the historical circumstances as the cause of regional differences. In the North-Eastern part of Lithuania the settlements are smaller than in the Western part of Lithuania. The analysis shows that the increasing importance of the centre-periphery factor will further determine the decline of rural settlements in peripheral territories in Lithuania.