The study was to explore the telomerase activity and the expression of hTERT, c-myc and bcl-2 mRNA during terminal differentiation of HL-60 cells induced by all trans-retinoic acid (ATRA) and to study the possible molecular mechanism. By use of the model of differentiated HL-60 cells induced by ATRA, the telomerase activity was determined by TRAP-PCR-ELISA and the expression of hTERT, c-myc, bcl-2 mRNA was detected by RT-PCR in differentiated HL-60 cells. The results showed that during differentiation of HL-60 cells, the telomerase activity was decreased, the expression of hTERT, c-myc and bcl-2 mRNA was downregulated, and the downregulation of hTERT occurred prior to suppression of telomerase activity. It is concluded that the telomerase activity is related to decrease expression of hTERT, c-myc and bcl-2 mRNA during HL-60 cell differentiation induced by ATRA.