The invention provides a method of establishing a gnotobiotic animal obesity model and an application of the model. According to the method, a gnotobiotic animal obesity model is established by inoculating an LPS (lipopolysaccharides) producing strain under a high-fat diet condition. When a germfree animal is fed with high-fat diet, a microorganism such as LPS producing strain or a combination thereof is inoculated, then the microorganism can colonize in the intestinal tract of the germfree animal, and the animal shows symptoms of disorder of the systems of metabolism, immunity and the like such as obesity, insulin resistance and chronic inflammation at the same time. The invention also relates to a method for screening the microorganism involved in obesity and combination thereof and providing a drug target for treating obesity and a method for screening the microorganism with an effect of preventing and treating metabolic diseases such as obesity, and provides a new method for treating obesity and the method provided by the invention can be applied to the screening and effect evaluation on foods (formula), medicines, nourishments, healthcare products, beverages and the like with an effect of preventing and treating metabolic diseases such as obesity.