Objective To detect microsatellite instability(MSI) in transgenic(Tg) mice and spontaneously mutated (SM) inbred mice. MethodsAccording to the references, we selected198 microsatellite loci from 19 autosomes and X chromosomes of mice in GenBank. These loci are rich in polymorphic of mice. Then the comparative analysisof microsatellite DNA polymorphism in 6 Tg strain and 5 SM strain of mice and wild-typecontrol mice was conducted through PCR amplified. The analysis of microsatellite DNA polymorphism was undergone through 1.5% agarose gel electrophoresis and STR scanning. Results We found 40 microsatellite loci showed MSIafter the genetic modification compared to the wild type control mice.In the spontaneously mutated mice, 55.6% (10/18) changed from homozygous to heterozygous (type I), whereas three loci (16.6%) of these mice experienced homozygous mutations (type II). Five loci (27.8%) had both types of mutations. In the Tg animals, however, most of the CMP genotypes (87.5%, 28/32) were changed from homozygous to heterozygous mutations (type I), whereas only two loci (6.2%) of the micepossessed homozygous mutations (type II). Moreover, two loci harbored both types of mutations. Conclusion We primarily confirmed that gene-modify can result in MSI. Some microsatellite loci are more sensitive to genetically modification