Due to the complex topography of Yunnan-Guizhou Plateau (YGP), the spatiotemporal differences of aerosol regional distribution are worthy of discussion, which is of great significance for the ecological civilization in different regions. By using spatial interpolation and trend analysis methods, the aerosol optical depth (AOD) regional distribution and climatic characteristics of YGP from 2001 to 2016 were analyzed with MODIS AOD data in 3 km resolution. The AOD data in fine resolution of 3 km aerosol indicated the different characteristics of spatial gradient distribution and temporal variations of aerosol distribution over the plateau. Taking Wumeng Mountains as the boundary of YGP, the annually averaged AOD spatial distribution over the plateau showed a "high in the East and low in the west" pattern, with the annual AOD average of 0.32 in the east and 0.13 in the west. The high value area of annual AOD average (>0.6) was located in the north of Guizhou province adjacent to Sichuan Basin (including Zunyi and Tongren), the southeast adjacent to Guangxi province, Guiyang and Kunming. The distribution of high value area was mainly affected by human activities, regional transport and topography. Over the past 16 years, the annual AOD averages over the YGP presented a downward trend, with a downward trend rate of-0.021/10a, with fluctuation rising from 2001 to 2011 and a significant decrease from 2011 to 2016 (the rate is-0.33/10a). The decline rate of AOD in eastern and western YGP was quite different, and the descending value in the eastern YGP was obviously higher than that in the western, with the change rates of-0.059/10a and-0.003/10a, respectively.