Aim To investigate the possible role of myocardin in the vascular remodeling of vascular smooth muscle cell (VSMC) induced by high cyclic tensile stress. Methods Using FX-5000T in vitro cyclic stretch loading system, the VSMC in vitro were stimulated by cyclic stretch with frequency of 1.25 Hz, loading amplitude of 5% (normal physiological state) and 15% (simulated hypertension state) for 24 hours; Western blot and real time RT-PCR were used to detect the protein expression level and mRNA level of myocardin, atrogin-1, SMA and SM22. The expression level of myocardin and atrogin-1 were measured after the treatment with proteasome inhibitor MG132. The alteration of myocardin, SMA and SM22 was measured after the knockdown of atrogin-1. Results Compared with 5% normal group, 15% cyclic stretch promoted the dedifferentiation of SMCs. Western blot showed that 15% of cyclic stretch decreased the protein le-vels of myocardin, SMA and SM22, and increased the protein expression level of atrogin-1. RT-PCR showed that the mRNA levels of myocardin, SMA and SM22 were down regulated, and the mRNA level of atrogin-1 was up regulated. The results showed that the protein levels of myocardin, SMA and SM22 increased after siRNA down-regulation of atrogin-1. The protein levels of myocardin, SMA and SM22 increased and the protein level of atrogin-1 decreased after treated with 1 μmol/L MG132. Conclusion High cyclic stretch can regulate phenotypic transformation of VSMC by regulating the expression of myocardin, an important transcription co-factor, thus affecting the differentiation and proliferation of VSMC.