Aim To investigate the relationship between tetrandrine(Tet) on prevention and treatment of restenosis and phenotypic modulation of vascular smooth muscle cells(VSMC) as well as its signal transduction pathway after vascular intimal injury. Methods HE staining was used to analyse vascular morphology change at sham-injured,injured and Tet-treated group 28 days.Immunohistochemistry and Western blot were respectively used to detect the expression change of smooth muscle α-actin(SM α-actin) and proliferation cell nuclear antigen(PCNA),p38 in injured group and Tet group at 7,14 and 28 days after balloon injury. Results The every layer structure in vascular wall of sham-injured artery was intact.Neointimal area was obviously increased and lumen area was notably decreased in injured group.In the Tet group the intimal proliferation was showed but notably weaker than that of the injured group and lumen area notably increased.Compared with the injured group,the expression of SM α-actin,PCNA and p38 in vascular wall of the Tet group was not significantly different and neointimal proliferation degree was also basicly the same at 7 days after injury.The expression of PCNA and p38 in Tet group was all significantly lower than that in injured group in vascular wall at 14 and 28 days after injury.However,expression of SM α-actin in Tet group was slightly higher than that in injured group at 14 days, and not significantly different between the two groups at 28 days. Conclusion Tet could reduce neointimal hyperplasia by inhibiting VSMC phenotypic modulation and its signal transduction.