The nest flea index of Meriones unguiculatus is a critical indicator for the prevention and control of plague, which can be used not only to detect the spatial and temporal distributions of Meriones unguiculatus, but also to reveal its cluster rule. This study used global spatial autocorrelation and spatial hot spot detection methods to describe the relationship between different years and the autocorrelation coefficient of nest flea indexes; it also used a spatial detection method and GIS technology to detect the spatial gathered hot spot of Meriones unguiculatus in the epidemic areas. The results of this study showed that (1) there were statistically significant spatial autocorrelations in the nest flea indexes in 2006, 2012, 2013 and 2014. (2) Most of the distribution patterns of Meriones unguiculatus were statistically significant clusters of high values. (3) There were some typical hot spot regions of plague distributed along the Inner Mongolia plateau, north of China. (4) The hot spot regions of plague were gradually stabilized after increasing and decreasing repeatedly. Generally speaking, the number of hot spot regions showed an accelerated increase from 2005 to 2007, decreased slowly from 2007 to 2008, rapidly increased again after decreasing slowly from 2008 to 2010, showed an accelerated decrease from 2010 to 2011, and ultimately were stabilized after rapidly increasing again from 2011 to 2014. (5) The migration period of the hot spot regions was 2–3 years. The epidemic area of plague moved from southwest to east during 2005, 2007, 2008 and 2010, from east to southwest during 2007 and 2008, from east to west during 2010 and 2011, and from Midwest to east during 2011 and 2014. (6) Effective factors, such as temperature, rainfall, DEM, host density, and NDVI, can affect the spatial cluster of Meriones unguiculatus. The results of this study have important implications for exploring the temporal and spatial distribution law and distribution of the hot spot regions of plague, which can reduce the risk of plague, help support the decision making process for the control and prevention of plague, and form a valuable application for plague research.