The aim of the present study was to determine the effects of grape skin which was well known as natural antioxidant using 3T3-L1 adipocyte, representative cells with morphological and biochemical characteristics of adipocytes. Grape skin extract (GSE) suppressed the differentiation of 3T3-L1 adipocytes, and decreased the triglycerides content with lipid accumulation. The adipogenesis inhibitory effect of GSE was confirmed in adipocyte hormone secretion, such as leptin and adiponectin, as well as glycerol-3-phosphate dehydrogenase activity. However, apoptosis of both mature pre-adipocytes and adipocytes was not induced by GSE. The level of gene and protein expression was observed to understand the antiobesity mechanism underlying GSE. GSE treatment of 3T3-L1 cells resulted in decrease in the adipogenic transcription factor ($PPAR{gamma}$, $C/EBP{alpha}$, and SREBP1) gene and protein expression, and preadipocyte secreted factor-1 mRNA was up-regulated compared to the adipocyte control. The lipolysis-related mRNA level (hormone-sensitive lipase, lipoprotein lipase, and perilipin) in adipocytes with the addition of grape skin was similar to preadipocytes. These results support the potential application of GSE as a natural anti-obesity material in the food industry.