Chinese mitten crab (Eriocheir sinensis) is a very importantly native species in China. However, this species had been introduced to Europe and North America and had posed great influences on invaded ecosystems because of their rapid expansion. In this study, genetic variation and diversity of the Chinese mitten crab from its native ranges (Yangtze and Yellow Rivers in China) and colonized regions (Elbe River in Germany, Rhine River in Netherlands, Thames River in UK and San Francisco Bay in USA) were investigated using twenty microsatellites loci. The results found that the native populations possess higher genetic diversity than the colonized populations, and significant genetic differentiation between the native and colonized populations, and among the colonized populations. Bayesian clustering analysis showed significant genetic cluster of the colonized population from the native populations, and also significant genetic variation between the North American and European populations. Principal component analysis (PCA) indicated the high level of genetic differentiation between the native and colonized populations. Bottleneck signal test showed that the Rhine River experienced significant bottleneck effect. The results indicated that adaptive evolution would have occurred in Chinese mitten carp during its colonized process.