Objective：The aim of this study was to investigate the potential effects and mechanisms of low-intensity pulsed ultrasound（LIPUS） on the metabolism of hypertrophic adipose tissue induced by high-fat diet. Methods：C57BL/6J male mice were fed with a high-fat diet containing 60% kcal fat for obese mice model，and then 10 obese mice were selected to receive LIPUS irradiation at the groin fat pad for 10 weeks. The body weight of mice and inguinal fat at target area were weighed. Peripheral venous blood was drawn for the blood lipid test，complete blood counts and plasma biochemical profile. Safety tests of LIPUS were conducted on the basis of skin and muscle sections at LIPUS site with HE staining. And target fat stained with HE was used to observe the size of adipocytes. The content of triglycerides in the target fat pad was measured by glycerol phosphate oxidase-p-aminophenazone methods. The mRNA expression levels of transcription factors for adipogenic differentiation，lipolytic enzymes and their transcription factors at the LIPUS region were analyzed by qPCR. Additionally，Western blot was applied to detect the protein levels of transcription factors for adipogenic differentiation，lipolytic enzymes，and their related signaling pathways. Results：LIPUS irradiation significantly reduced fat weight，triglyceride content and adipocyte size in the target area of obese mice that received 77.20 mW/cm2 LIPUS treatment. Meanwhile，LIPUS down-regulated the expression of transcription factors for adipogenic differentiation in the target region. Expressions of lipolysis related signaling pathways and lipolytic enzymes were up-regulated via LIPUS stimulation. In addition，preliminary results indicate that LIPUS has a good safety profile at current dose. Conclusion：LIPUS diminishes local adipose tissue hypertrophy induced by high-fat diet through inhibiting adipogenic differentiation and encouraging lipolysis procedure.