Objective: In order to assess the genetic stability of doxorubicin resistance sarcoma S-180R cell line in vivo.Methods: The drug resistant genes and molecules were examined by flow cytometry, South blot, North blot and RT-PCR. Results: The results showed that drugefflux in S-180R increased nearly 100-folds, as compared with its parent cells, the rate of half peak width resistant cell/peak high decreased from 0.56 to 0.23 measured by flow cytometry after two years. The mdr1 gene amplified and overexpressed significantly in S-180R and the expression of topoisomerase Ⅱα gene decreased remarkably in S-180R. There was no significant different of the MRP expression between S-180R and S-180.Conclusion: These results indicated that drug resistance of S-180R was maintained and also increased. The major mechanism of drug resistance is the amplification and overexpression of mdr1 gene, the decreased expression of topoisomerase Ⅱα also contributed to it. So, S-180R is an ideal experimental model for the study of doxorubicin resistance and its reversion in vivo.