Aim or purpose: This study aims to explore the effect of miR-21 on osteoclastic differentiation and proliferation of macrophage RAW264.7. Materials and methods: RAW264.7 cells were transfected by lentiviral vector and divided into 4 groups: osteoclastic differentiation: OC marker genes (Ctsk, Mmp9, Acp5 and Nfatc1) were detected by RT-qPCR. Western blot was performed to detect the expression levels of Ctsk, Mmp and Pdcd4. proliferation: The optical density of the cells in each group were detected by CCK-8 at 1, 3, 5 and 7 days. The cell cycle of each group was detected by flow cytometry. Results: After overexpression of miR-21, the number of osteoclasts, enzyme activity and concentration of TRAP, OC marker genes and Ctsk and Mmp9 were significantly increased, while the expression of Pdcd4 was down-regulated. However, the outcome is contrary after inhibition of miR-21 expression. There was no significant difference in RAW264.7 cell proliferation cycle and optical density at 1, 3, 5 and 7 days. Conclusions: MiR-21 can promote differentiation of RAW264.7 cells in vitro, and this process may be realized by regulating the expression of Pdcd4; and there was no significant effect of miR-21 on the proliferation of RAW264.7 cells.