Aim To investigate the cellular signal transduction pathway of vascular smooth muscle cell (VSMC) proliferation stimulated by oxidized low density lipoprotein (ox LDL). Methods Rabbit aortic VSMC was cultured in 3 groups:control, low density lipoprotein (LDL), and ox LDL. Cell proliferating ability was determined by measuring cell number and mitochondrial dehydrogenase activity (MTT assay). Western blotting was used to detect the protein expression of phosphotase and tensin homology deleted on chromosome ten (PTEN). Phosphate concentration released from PTEN specific substrat diC 16 PIP 3 was assessed using green reagent method. Results ox LDL (50 mg/L) increased cell number and MD activity to 1.78～3.21 fold, but the same concentration of LDL has no such mitogenic effect. Phosphatase activity detection shew that the dephosphate action of PTEN was inhibited by ox LDL (20～50 mg/L) in a concentration dependent manner,and this inhibiting effect was at its maximum within 10 min,lasting at least for 24 h (p<0.01, vs. control group). Conclusion Ox LDL improved VSMC proliferation probably by inhibiting the lipid phosphatase activity of PTEN.