Objective: To study the effects of tetrandrine (Tet) on phenotypic modulation of vascular smooth muscle cells (VSMCs) and expression of p38 mitogen-activated protein kinase (p38MAPK) as well as mitogen-activated protein kinase phosphatase-1(MKP-1) after vascular intimal injury. Methods: HE staining was used to analyze vascular morphology of sham-injured group, injured group and Tet-treated group at day 28. Immunohistochemistry, Western blot and RT-PCR were respectively used to detect the expression change of smooth muscle α-actin (SMα-actin), proliferation cell nuclear antigen (PCNA), p38MAPK and MKP-1 of injured group and Tet neointimal area was significantly increased and the lumen area notably decreased in injured group at day 28. The neointimal proliferation in Tet treated group was less than that in injured group, and the lumen area of Tet group was significantly increased than that of injured group was no difference, and the neointimal proliferation condition was also basically as same as injured group at day 7 after injury. The expression of PCNA and p38MAKP in Tet group was obviously lower than that in injured group, and the expression of MKP-1 in Tet group was obviously higher than that in injured group at days 14 and 28 after injury. The expression of SMa-actin in Tet group was slightly higher than that in injured group at days 14 and 28 after injury. Conclusions: Tet could reduce neointimal proliferation by inhibiting VSMCs phenotypic modulation and p38MAPK signaling transduction pathway as well as its down regulation.