Arsenic compounds are serious harm to human health. Skin damages, cardiovascular disease, diabetes and cancer may cause by chronic arsenic exposure. Arsenic metabolism pattern is an important index of arsenic poisoning, our previous studies have shown that exogenous factors play a more important role in arsenic poisoning than environmental factors. Based on this, the focus of this research is folic acid which are important cofactors in methionine cycle. In the present study, we establish high arsenic exposure animal model and then applying interference factors. Our results show that As levels were significantly dose-dependent in different experimental groups, as well as moderate increase of SAH, decrease of SAM and SAM/SAH were found in the blood by sub chronic arsenic administration. We also observed the involvement of folate in promoting arsenic methylation in vivo. Furthermore, SAM level increased after the treatment of folate.