The Tarim River (TR), as the longest inland river at an arid area in China, is a typical regions of vegetation variation research and plays a crucial role in the sustainable development of regional ecological environment. In this paper, the newest dataset of MODND1M NDVI, at a resolution of 500m, were applied to calculate vegetation index in growing season during the period 2000-2015. Using a vegetation coverage index, a trend line analysis, and the local spatial autocorrelation analysis, this paper investigated the landscape patterns and spatio-temporal variation of vegetation coverage at regional and pixel scales over mainstream of the Tarim River, Xinjiang. The results showed that (1) The bare land area on both sides of Tarim River appeared to have a fluctuated downward trend and there were two obvious valley values in 2005 and 2012. (2) Spatially, the vegetation coverage improved areas is mostly distributed in upstream and the degraded areas is mainly distributed in the left bank of midstream and the end of Tarim River during 2000-2005. (3) The local spatial auto-correlation analysis revealed that vegetation coverage was spatially positive autocorrelated and spatial concentrated. The high-high self-related areas are mainly distributed in upstream, where vegetation cover are relatively good, and the low-low self-related areas are mostly with lower vegetation cover in the lower reaches of Tarim River.