The free flaps were harvested to evaluate flap necrosis and neovascularization after 2 h or 7 d of reperfusion. p-CaSR/CaSR was extensively expressed in vascular endothelial cells of free flaps after I/R injury, and activation of the SDF-1<i>α</i>/CXCR4 axis and NPS2143 could reduce the expression of cleaved caspase-3, caspase-9, FAS, Cyt-c, and Bax and increase Bcl-2 expression; the opposite was true after CaSR activation.