<b><i>Background:</i></b> Bisphenol A (BPA) is a ubiquitous endocrine disrupting chemical and obesogen. Although limited evidence exists of the effects of BPA on hypothalamic agouti-related peptide (AgRP) levels, the mechanisms underlying these effects remain unknown. Given that AgRP is a potent orexigenic neuropeptide, determining the mechanism by which BPA increases AgRP is critical to preventing the progression to metabolic disease. <b><i>Methods:</i></b> Using quantitative reverse transcriptase polymerase chain reaction, we investigated the response of <i>Agrp</i>-expressing mouse hypothalamic cell lines to BPA treatment. The percentage of total BPA entering hypothalamic cells in culture was quantified using an enzyme-linked immunosorbent assay. In order to identify the mechanism underlying BPA-mediated changes in <i>Agrp</i>, siRNA knockdown of transcription factors, FOXO1, CHOP, ATF3, ATF4, ATF6, and small-molecule inhibitors of endoplasmic reticulum stress, JNK or MEK/ERK were used. <b><i>Results:</i></b> BPA increased mRNA levels of <i>Agrp</i> in six hypothalamic cell lines (mHypoA-59, mHypoE-41, mHypoA-2/12, mHypoE-46, mHypoE-44, and mHypoE-42). Interestingly, only 18% of the total BPA in the culture medium entered the cells after 24 h, suggesting that the exposure concentration is much lower than the treatment concentration. BPA increased <i>pre-Agrp</i> mRNA levels, indicating increased <i>Agrp</i> transcription. Knockdown of the transcription factor ATF3 prevented BPA-mediated increase in <i>Agrp</i>, <i>pre-Agrp</i>, and in part <i>Npy</i> mRNA levels. However, chemical chaperone, sodium phenylbutyrate, JNK inhibitor, SP600125, or the MEK/ERK inhibitor PD0352901 did not block BPA-induced <i>Agrp</i> upregulation. <b><i>Conclusion:</i></b> Overall, these results indicate that hypothalamic <i>Agrp</i> is susceptible to dysregulation by BPA and implicate ATF3 as a common mediator of the orexigenic effects of BPA in hypothalamic neurons.