This study is aimed at identifying of depopulated rural settlements over a quarter century since 1365 (1986) by 1390 (2011) in Isfahan province and representing a geographically interpretation of the phenomena, using statistical methods and spatial analysis in the geographic information system environment. To do this, at first, layers of the spatial distribution of settled villages of 1365 and identified depopulated ones over the two and a half decades period of the study have based on the detailed reports of public censuses’ results of Iran statistical center identified and prepared in ArcGIS environment. Afterwards, the rural settlements exodus analyzed based on the prepared, corrected and classified natural parameter layers of altitude, slope, aspect, temperature, land types and distance from wells and springs, spatially. Definition and calculation of two spatio-statistical indicatorsdad been the basis of analysis; “the settled villages density at the beginning year of 1365” and “relative percent of depopulated villages over the study period with respect to the total beginning settled ones”. The indicators calculated for each of the layers’ zones using the “zonal mean statistic” function from the spatial analyst tool of ArcGIS and analyzed statistically by correlation and Chi-Square tests. Results revealed that there is a significant relationship between exoduses and natural factors of slope, land types, altitude and distance from wells respectively. While that was not true for aspect parameter. The influence knowhow of natural factors on rural exodus, helps the landuse planning projects to more consider them and ensure the more stability of rural settlements agains the more exodus in the future.