Objective：Bone marrow derived mesenchymal stem cells（MSCs）in bone marrow microenvironment was found to be involved in the chemoresistance of myeloma cells. In this study，we investigate the role of IL-1β or TNF-α-treated bone marrow MSCs in chemosensitivity of myeloma cell line H929 to doxycycline（DOX）in vitro，and find some possible mechanisms. Methods：CCK8 assay was employed to measure the proliferative rate of H929 cells in the presence of DOX at different concentration，either alone or co-culture with bone marrow MSCs pretreated with IL-1β or TNF-α or not. The apoptotic ratio of H929 cells treated with DOX in the presence of IL-1β or TNF-α-treated bone marrow MSCs or not was determine by flow cytometry（FCM）. FCM was also used with real time fluorescence quantitative polymerase chain reaction（RT-qPCR）to measure vascular cell adhesion molecule type one（VCAM-1）on MSCs. The p-Erk1/2 expression level in H929 was measured by Western blot. Results：DOX inhibited the proliferation and induced apoptosis of H929 in a time and dose-dependent manner. IL-1β or TNF-α-pretreated bone marrow MSCs reduced the cytotoxic effects of DOX in H929 cells. Expression level of p-Erk1/2 was down-regulated in H929 cells in the presence of DOX treatment，and this down-regulating effect of DOX was most pronounced when H929 cells were co-cultured with IL-1β or TNF-α-pretreated bone marrow MSCs. In addition，we found that VCAM-1 expression of bone marrow MSCs was up-regulated by IL-1β or TNF-α treatment. Conclusion：DOX was shown to have cytotoxicity to myeloma cells line H929 in a time and dose-dependent manner in vitro. IL-1β or TNF-α could abrogate the cytotoxic effects of DOX in H929 cells indirectly via bone marrow MSCs. Erk pathway in H929 cells and VCAM-1 expression on MSCs may be involved in this myeloma-protective effects by IL-1β or TNF-α.