K562 cell line has been used as a model of common progenitor of erythroblasts and magakaryocytes and can be differentiated into erythroid and megakaryocytic lineages by hemin and phorbol myristate acetate (PMA) respectively. We analyzed mRNA expression in un-induced, hemin-induced and PMA-induced K562 cells by differential display reverse transcription polymerase chain reaction (DDRT-PCR) method. 314 differential expression sequence tags (ESTs) were obtained. Among them, 201 ESTs displayed up-regulation and 85 ESTs down-regulation after hemin induction, 186 ESTs showed up-regulation and 72 ESTs down-regulation after PMA induction. The differentially expressed genes included those encoding transcription factors, signaling factors, apoptosis-associated factors and others. 45 of these ESTs stand for genes whose open reading frames were found but whose functions remain unknown. 4 ESTs represent possibly new genes. Furthermore we compared differences of gene expression during hemin-induced erythroid differentiation and PMA-induced megakaryocytic differentiation and found that the expressional changes of some transcription factors and metabolism proteins are the common but the expressional changes of some signal pathways in these two differentiation processes are different. These results suggested that erythroid differentiation and megakaryocytic differentiation are associated in activation and repression of different signal pathways.