Objective To investigate the effect and underling mechanism of genistein(GEN)on adipogenesis in 3T3-L1 preadipocytes.Method 3T3-L1 preadipocytes were induced to differentiate in the presence of vehicle(MDI),GEN or SB203580.On D 6 after induction of differentiation,lipid accumulation was assessed using the dye Oil Red O,medium was collected and assayed for the content of NEFA and TG,and fatty acid synthase(FAS) expression was analyzed by Western blotting.After pretreatment with GEN for 30 min,3T3-L1 preadipocytes were stimulated with insulin for 5 or 10 min.The phosphorylation of p38 MAPK(p38) was analyzed by Western blotting.Results GEN inhibited lipid accumulation and decreased NEFA and TG content of 3T3-L1 on D 6 after the induction of differentiation.Pretreatment with GEN inhibited phosphorylation of p38 when stimulated with insulin.Furthermore,GEN inhibited the expression of FAS.SB203580,a p38 inhibitor,mimicked the FAS inhibition effect of genistein,which suggested that the inhibitory effect of GEN on FAS was partially via the p38 pathway.Conclusion Geinstein attenuates the differentiation of 3T3-L1 via the inhibition of p38 and FAS.