In present study, we showed that EGF activated MEK/ERK and PI3K/AKT signaling cascades to down-regulate miR-124a expression, and a member of ETS family of transcription factors, ETS2, acted as the downstream effector of EGFR signaling to suppression the promoter activity of miR-124a (a kind of miRNA that related to beta cell dysfunction in diabetes). The gene discussed is EGFR; the disease is diabetes mellitus.