Desertification is one of the main environmental and also social and economic problems facing Iran. Seventeen out of 31 Iranian provinces, which are home to approximately 70% of the total population, are affected by Desertification. This study aimed to use GIS and fuzzy logic for mapping environmentally sensitive areas (ESAs) to desertification based on MEDALUS approach in Isfahan province, central Iran. Six desertification indicators including climate, soil, vegetation, soil erosion, groundwater, and management and policy quality were used to determine various types of ESAs to desertification. Seventeen desertification indices affecting the quality of each indicator were spatially mapped and assigned a value between 0 and 1 using fuzzy logic option of ArcSDM3 software in GIS environment. Results showed that a 21.7% of the study area was classified as critical, 70% as fragile, 5.5% as potential and 2.9% of the area was not affected by desertification. In the town of Borkhar 64.2% of the area was classified as critical, followed by the town of Isfahan and Nayin with 40.2%, 31.8%, respectively. Results at provincial scale indicated that the climate indicator and humidity index with a weighting mean of 0.71 and 0.77 were the most affective factors in the desertification of the study area. The developed model in this study can be used for mapping Desertification status in other 16 provinces which contain desert areas. These assessments provide a GIS-based desertification database which Iran as a member of UNCCD can use to report the condition of Desertification at national scale.