Objective To investigate effects of the cyclic stretch on rat bone marrow mesenchymal stem cells (rBMSCs) proliferation and the related signal molecules. Methods The cyclic mechanical stretching apparatus was used to study the effects of the cyclic stretch on the growth of rBMSCs with different parameters. The expression of c fos was measured by RT PCR at mRNA level and the levels of phosphorylated extracellular signal regulated kinase 1/2 (p-ERK1/2), total ERK1/2 (t-ERK1/2) and c-fos proteins were detected by Western blotting. Results The proliferation of rBMSCs could be stimulated by the cyclic stretch, and the number of cells was increased to 1.4 times compared with that of the control group at 1 Hz, 10% strain for 15 min and then being static for 6 h. Moreover, the expressions of c-fos mRNA and protein levels were increased significantly after the stimulation of the stretch. On the other hand, it was found that the cyclic stretch could remarkably enhance the phosphorylation of ERK1/2, but did not influence the level of t-ERK1/2. After treated with PD98059, the proliferation of rBMSCs stimulated by the cyclic stretch was inhibited prominently in a dose dependent manner and the expressions of p-ERK1/2, as well as c-fos at gene and protein levels were sharply down regulated. Conclusions ERK1/2 signal molecules play an important role in regulating the cyclic stretch on the proliferation of rBMSCs and transcription factors may take part in the regulations during this progress.