Adipocyte differentiation is regulated by the sequential activation of transcription factors such as the CAAT/enhancer binding protein and peroxisome proliferator- activated receptor-gamma (PPAR-gamma). Several recent studies have shown that regulators of chromatin structure are also involved in adipocyte differentiation. Here we investigated the effects of diallyl disulfide (DADS), an oil-soluble sulfur compound found in processed garlic and an inhibitor of histone deacetylase (HDAC), on adipogenesis. Treatment with DADS accelerated terminal differentiation of 3T3-L1 cells into adipocytes as evidenced by Oil red O staining and cellular triglyceride assay results. Notably, the inhibition of HDAC during the first 2 days was sufficient to stimulate adipogenesis. Western blot analysis revealed that DADS increased the level of acetylated histones H3 and H4. In addition, DADS increased the expression of adipogenesis-related genes; LPL, FAS, SREBP1c, aP2 and PPAR-gamma, and decreased the expression of pref-1, a preadipocyte marker gene. Taken together, our results suggest that DADS affects adipocyte differentiation through histone acetylation at an early phase of adipocyte differentiation.