Aim To observe whether the proliferation and apoptosis of mouse vascular smooth muscle cells(VSMC) were induced by stretch stress (SS) via PKCα phosphorylation and to investigate the role of berberine (BBR) and related mechanism on the process. Methods The experiment was divided into six groups:normal control(NC) group, BBR group, PKCα inhibitor (Go6976) group, SS group, SS+BBR group and SS+Go6976 group. VSMC were pretreated with BBR or Go6976 for 1 h, and stimulated for 15 min with SS at 10% amplitude. PKCα and MAPK (ERK, JNK, p38) phosphorylation were measured by Western blot. After pretreated by BBR or Go6976, and SS stimulation for 1 h, the proliferation (Ki67) and apoptosis (TUNEL) of VSMC were measured by immunofluorescence. Results Compared with the NC group, SS could increase the phosphorylation levels of PKCα and MAPK(ERK, JNK, p38) (P＜0.05), and increase the levels of VSMC proliferation and apoptosis (P＜0.05). BBR could inhibit the phosphorylation levels of PKCα and MAPK (P＜0.05), while inhibiting VSMC proliferation and apoptosis (P＜0.05); Go6976 could inhibit PKCα, ERK and JNK phosphorylation (P＜0.05), but had no effect on the phosphorylation increase of p38, while inhibiting VSMC proliferation and apoptosis (P＜0.05). Conclusion BBR inhibits the phosphorylation of PKCα and MAPK (ERK, JNK, p38) induced by SS, and further inhibits the proliferation and apoptosis of VSMC.