The invention discloses a preparation method of an imidazole-[1,2-a]-pyridine derivative, and belongs to the field of organic synthesis. The preparation method comprises the following steps of using 2-phenoxyacetophenone as a starting raw material, using elemental iodine as a catalyst, and reacting with the 2-phenoxyacetophenone; separating by column chromatography, so as to obtain the imidazole-[1,2-a]-pyridine derivative. Compared with the prior art, the preparation method has the advantages that the reaction yield rate is high, the post-treatment is simple, and the preparation method is more suitable for industrialized production. The prepared imidazole-[1,2-a]-pyridine derivative can be used as a medicine precursor, be used for synthesizing antifungal, anti-inflammatory, antitumor, antivirus, antibacterial, antiprotozoal, antipyretic, analgesic and antiapoptotic medicines and the like, and be applied to the fields of organic photoelectric materials, medicines, biological probes, fluorescent dyes and the like.