The invention provides a prepolymer of 4,2'-methyl diphenylene diisocyanate (MDI) and 4,4'- methyl diphenylene diisocyanate (MDI) as a curing agent, and a preparation method thereof. The method comprises the following steps: 4,4-MDI and organic solvent are added to a reaction kettle, heated to between 50 an d 90 DEG C and added with dehydrated polyol, and then react for 2 to 4 hours so as to prepare 4,4-MDI modifier; a mixture of 4,2'-MDI and 4,4'MDI is added and then cooled; and trimethylolpropane and the organic solvent are dripped and thermally insulated, and react for 1 to 6 hours, so as to obtain a product. The method modifies the 4,4-MDI and then blends the 4,4-MDI with the mixture of 4,2'-MDI and 4,4'-MDI and TMP for pre-polymerization, thereby solving the problem of manufacturing the prepolymer with two isomers of MDI in an arbitrary proportioning form. A series of produced prepolymers can meet different requirements of coatings and adhesives in the polyurethane industry on the curing agent, and have the advantages of wide application range, high strength, low toxicity, adjustable room-temperature curing speed, good storage stability, capability of obtaining the products with high solid content, and the like.