In this paper, the Carnegie-Ames-Stanford Approach (CASA) model, which was based on the theory of Resource Balance and Light Use Efficiency, was proposed to simulate Net Primary Production (NPP) of different vegetation types in the Tianshan Mountains Region (TMR) over the past few decades and its response to climatic factors. The inputs of the model include a set of monthly MODIS NDVI product data & meteorological interpolation data from 2001 to 2013 in this region. China Land use/cover data in 2005 was used to confirm the light utilization efficiency of different vegetation types. The process of the model was fulfilled by compiling programs with IDL in ENVI 5.1. The outputs of the model embrace annual NPP & NPP summation. In order to verify the simulation precision of the model, comparing with other NPP simulation results which research in similar regions by using different models. The results shows that, the spatial distribution of vegetation NPP in the TMR, by and large, decreased from west to east and increased from north to south. Average annual NPP (by C, the same below) and total NPP from 2001 to 2013 in TMR was 156.63 g·m~(-2)·a~(-1) and 93.2 Tg·a~(-1) respectively. The vegetation NPP in the TMR showed a slowly increasing trend from 2001 to 2013. Among them, NPP rapid growth area scattered across the north slope of the forest and cropland in the TMR, with the growth rate of 25~55 g·m~(-2)·a~(-1). The total NPP of grassland fluctuated obviously, forest and cropland had a increasing tendency slowly, while the total NPP of desert tended to be gentle. The average correlation coefficients of vegetation NPP with annual rainfall and annual mean temperature were 0.383 and -0.189. The response of NPP to annual rainfall is more sensitive than to the annual mean temperature in the study area. Rainfall is the major factor which affected the growth of vegetation in the TMR. There were significant differences in response of different types of vegetation NPP to climatic factors. The vegetation NPP of forest, grassland and desert in the TMR was mainly affected by rainfall, while NPP of cropland was limited both by rainfall and temperature.