Anti-obese effects of an ethanol extract of Elsholtzia ciliata (Elsholtzia ciliata extract, ECE) in high-fat diet-induced obese mice were investigated. The body weight gain, weights of adipose tissues, and adipocyte size were reduced in ECE-treated obese mice compared to those in high-fat diet-induced obese mice. ECE treatment also resulted in significant decreases in serum total cholesterol, triglyceride, and leptin concentrations, relative to concentrations in untreated obese mice. Furthermore, ECE significantly suppressed the elevated mRNA expression levels of peroxisome proliferator-activated receptor ${gamma}$, fatty acid synthase, and adipocyte fatty acid-binding protein in the subcutaneous adipose tissue of obese mice. In addition, ECE treatment inhibited 3T3-L1 preadipocyte differentiation and fat accumulation. These results suggest that ECE ameliorated high-fat diet-induced obesity by downregulating expression of some lipogenesis-related genes in the fat tissue of mice.