In order to explore the molecular mechanisms of sodium butyrate and trichostatin A onK562 cell proliferation/differentiation, K562 cells were grown in the absence or presence of sodiumbutyrate or trichostatin A. The percentage of viable cells was determined by trypan blue exclusion.Differentiation was determined by nitro-blue tetrazolium (NBT) reduction and cell surface adhesionmolecules analyzed by FACS. Cell cycle distribution was studied after DNA staining by propidium i-odide. Cell cycle regulatory proteins were detected by Western blot and reverse transcription-poly-merase chain reaction. The results showed that sodiun butyrate blocked cells mainly at the G0/G1phase of the cell cycle, whereas trichostatin A arrested the cells at G2 phase. Sodium butyrate coulddown-regulate the mRNA expression of cyclin D1, but not affect its protein expression; down-regu-late the protein expression of cyclin D3, but not affect its mRNA expression. Trichostatin Ashowed similar effects on cyclin D1 and D3 as sodium butyrate. Both sodium butyrate and trichosta-tin A could stimulate p21 expression of K562 cells at mRNA and protein levels. It m ay be concludedthat sodium butyrate and trichostatin A could promote the proliferation/differentiation of the K562cells, which might be contributed to the induced expression of cyclin D3 and p21 proteins.