Inhibiting CXCL12/CXCR4 axis with AMD3100 could significantly reduce atrial structural remodeling and AF susceptibility in AF model mice, mechanistically, via inhibiting the hyperactivation of pro-fibrosis signaling (ERK1/2 and AKT/mTOR) and inflammatory response (the recruitment of CD3+ T lymphocytes and F4/80+ macrophages). Here, CXCR4 is linked to atrial fibrillation.