Objective To investigate the effects of methoxychlor (MXC) exposure on the expression of estrogen receptor α (ERα) mRNA in mouse placenta during early pregnancy. Methods Pregnant mice were randomly divided into three groups with 10 for each, in which subcutaneous injection of MXC as the exposure group, subcutaneous injection of sesame oil as the normal control group, subcutaneous injection of estradiol (E2) as a positive control group. Placenta tissues were obtained from each group for analysis of ERα mRNA expression by using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results The expressions of ERα mRNA were significantly diferent between the MXC exposure group(0.68 ±0.11) and the positive control group(0.60±0.10) (P<0.05), but not diferent between MXC exposure group(0.68±0.11)and the normal control group(0.49±0.09)(P>0.05). Immunohistochemistry showed that the expression of ERα in pregnant mouse placenta exposed to MXC was significantly higher than that in the normal control group. Conclusions The expression of ERα in pregnant mouse placenta exposed to MXC is significantly increased, which may be one of the important mechanisms involved in the effects of MXC on embryonic development.