A micro-reaction device for preparing biodiesel by base catalysis includes a feeding system, a micro-reaction apparatus, and a separation apparatus. The feeding system is in communication with the micro-reaction apparatus, and the micro-reaction apparatus is in communication with the separation apparatus; the micro-reaction apparatus includes a micro-reactor, and the micro-reactor is a micro-dispersion micro-reactor; in the micro-reaction apparatus, an oil phase and short chain alcohols undergo an ester exchange reaction under base catalysis to generate fatty acid esters and by-product glycerol; and the micro-dispersion reactor is provided with a micro-dispersion structure for dispersing the short chain alcohols into micro-droplets. By the solution of the present application, the intrinsic safety of a process is improved, the reaction time is greatly shortened, the resistance to material flow is lower, the system operating pressure is low, and the single-channel treatment capacity is large, which is 10-500 times that of a micro-channel reactor.