Cyclin D2 was isolated as one of the genes expressed early in adipogenesis. The expression of cyclin D2 increased temporarily early on and then again late in the differentiation process. The expression of cyclin D1 and cyclin D3, the other D-type cyclins, was also transiently induced early during adipocyte differentiation. RNAi (RNA interference)-mediated knockdown of cyclin D1, D2, or D3 inhibited the differentiation of 3T3-L1 cells into lipid-laden adipocytes. Moreover, the knockdown of cyclin D1 or D3 significantly inhibited mitotic clonal expansion (MCE), while silencing of the cyclin D2 gene had a milder effect on MCE. Each of the D-type cyclins seems to play a crucial role in adipocyte differentiation by regulating MCE.