Abstract: Objective To study whether maternal exposure of perfluorooctane sulfonate(PFOS) relates with the alteration of DNA methylation level in liver of the offspring rats.Methods The pregnant rats were exposed to different doses of PFOS (control, 0.1, 0.6, and 2.0 mg/kg/d) during the gestational day of 2-21 by gavage.Then the rats were allowed to give birth to the offsprings and the livers of the offspring rats were collected 21 days after the birth.The total DNA methylation level,the methylation status of long inter spersed repetitive element-1(LINE-1) and the methy lation status of cytosine guanosine(CpG) island were evaluated with the global DNA methylation kit, bisulfite sodium process(BSP) combined cloned sequencing, and arbitarily primed polymerase reaction (APPCR), respectively.Results The global DNA methylation level at the highest dose group was significantly decreased(P<0.05).There were no significant differences in methylation levels of LINE-1 among the groups(P>0.05).The AP-PCR method showed significant difference in CpG island methylation among the three dose group compared to the control(P<0.05).In addition, the expression of DNA (cytosine-5-)methyltransferase 3 alpha(DNMT 3a) in the highest dose group was significantly increased (P<0.05).Conclusion In liver of offspring rats, the global DNA methy lation level and the status of CpG island methylation are related to prenatal exposure to PFOS.