Natural products such as caffeine have been found to be effective in reducing body weight through lipolysis . Here, we report the successful loading of caffeine onto dissolving microneedle following inhibition of its crystal growth by hyaluronic acid (HA), the matrix material of the dissolving microneedle (DMN). Further, the anti-obesity activity of caffeine was evaluated in high-fat diet-induced obese C57BL/6J mice. After 6 weeks of caffeine loaded dissolving microneedle patch (CMP) administration, lipolysis improved significantly as shown by leptin and adiponectin activity, which resulted in considerable weight loss of about 12.8 ± 0.75% in high-fat diet-induced obese mice . Comparison of the levels of triglyceride , total cholesterol, high-density lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol after CMP administration with the initial levels in obese mice indicated significant anti-obesity activity of CMP. These findings suggested that a novel CMP with an increased amount of caffeine loaded onto DMN has therapeutic activity against obesity.