Somatic cells can be reprogrammed into iPS (induced pluripotent stem) cells through the ectopic expression of defined transcription factors. However, the inefficiency and amount of time needed limited the potential application of iPS cells. We report an efficient method to generate iPS cells from MEF (mouse embryonic fibroblasts) through folate-depriviatoin, which was used to change the methylation of MEF. Without folate for 3 days, the induction efficiency is enhanced fivefold. Karyotype analysis showed that transient folate-depriving treatment did not negatively affect properties of iPS cells; characterised iPS cells show normal karyotypes. Thus, a new method has been found that can improve the induction efficiency, but not increase the chance of chromosomal mutation.