In this study, the scale effect on the interface reaction between PDMS-E emulsion droplets and gelatin was studied systematically. The monodisperse alpha-[3-(2,3-epoxy-71t. prop oxy) pr opyl]-w-butyl-p olydimethylsiloxane (PDMS-E) emulsion droplets on different scales were prepared using a.1 80 Shirasu porous glass (SPG) membrane with a 0.5 mu m pore size. The zeta potential results showed that the surface charge density of PDMS-E droplets decreased with the droplet scale, and the variation went through three stages, which corresponded to the diameter ranges of 100-450, 450-680, and 670-800 nm, respectively. The results of Raman spectra indicated that the distribution concentration of head groups in surfactants decreased but the polar epoxy groups tend to be exposed on the interface with the increase in the droplet scale. This was conducive to the nucleophilic attack of amino groups in gelatin on the epoxy group. Thus, the conversion of amino groups was related to the scale of the PDMS-E droplet. This study might provide a proper way to control the rate of interfacial reaction between immiscible macromolecule monomers.