The ingestion of edible seaweed has long been believed to be beneficial to human health due to its numerous biological actions. In the present study, the ethyl acetate fraction of a komulkosiraegi [Gracilaria vermiculophylla (Ohmi) Papenfuss] ethanol extract (GEFr) was found to potently inhibit adipogenesis of 3T3-L1 preadipocytes, decreasing triglycerol accumulation and the expression of peroxisome proliferator-activated receptor ${gamma}$ ($PPAR{gamma}$), members of the CCAAT/enhancer-binding protein (C/EBP) family, and fatty acid binding protein 2 (aP2). In mature adipocytes, GEFr was found to significantly activate AMP-activated protein kinase (AMPK) by activating liver kinase B1 (LKB1) and stimulating intracellular reactive oxygen species generation. The mRNA levels of genes involved in lipid catabolism were up-regulated. Also, GEFr increased lipolysis in a dose-dependent manner. Taken together, these results suggest that GEFr has potential for use in therapies designed to improve obesity.