Purpose: This study is to examine anti-obesity effect and cytotoxicity of the long-term oral administration of Ephedra Sinica(Ma-hwang, ES) Methods: Using diet-induced obesity C57BL/6 mouse model, anti-obesity effect and DNA chip expression and cytotoxicity of the long-term oral administration of this herbal extract were investigated. Results: The herbal extract treated groups were arrested in weight increment only when they were lodged together. Such effects were abolished when they kept individually. ES fed mice behaved very rudely and violently. On the basis of histological studies of liver tissues and also in vitro cytotoxicity tests of the liver and kidney cell lines, no significant toxicity was found by 14 weeks of ES treatments. However, we found significant changes in gene expression profile in ES treated group by micro-array analysis. In case of ES group, up-regulated genes were 113 and down-regulated were 120. Some of lipid metabolism related genes also significantly changed in treatment groups. Conclusion: ES had effects of increasing the basal metabolic rate by stimulating the sympathetic nervous systems.