The arid and semi-arid lands of Iran cover more than 70% of the country. Due to the broadness, remoteness, and harsh conditions of these lands, desertification assessment and monitoring using ground-based techniques appear to be limited. A study which was conducted in Isfahan province, Iran, evaluated the potential of different GIS techniques for assessing desertification severity in this region. According to the characteristics of the study area a regional model based on MEDALUS approach was developed using ArcGIS software. Six indicators including climate, vegetation cover, ground water, water and wind erosion, soil and management quality with 20 criteria were evaluated. Results showed that around 21.72% of the study area is classified as critical, 70.01% as fragile, 5.51% as potential and 2.89% of the area is not affected by desertification. Our results in this study provide a strong foundation for the use of GIS techniques as an adjunct to field methods for assessment and monitoring desertification status in this part of the world.