Abstract: AIM:To explore the protective effect of recombinant human pigment epithelium-derived factor (PEDF) on vascular smooth muscle cell (VSMC) proliferation and apoptosis after hypoxia/reoxygen (H/R). METHODS: VSMCs were primarily cultured by tissue-sticking method and were randomly divided into control group, H/R model group and model+PEDF group. According to the concentration of PEDF, the model+PEDF group was subdivided into 50-, 100-, 200- and 400-ng/ml groups. VSMC proliferation was determined by MTT and cell apoptosis was detected by Hoechst/PI staining and flow cytometry. Bcl-2 and Bax protein expressions were tested by Western blot. RESULTS: MTT showed that H/R increased VSMC proliferation and PEDF inhibited VSMC proliferation. The inhibitory effect of 200 ng/ml PEDF was the most significant. After VSMCs were treated with 100 and 200 ng/ml PEDF, Hoechst/PI staining and flow cytometry demonstrated that the apoptosis rate of the cells significantly increased (P<0.01 vs. control group and H/R).Western blot demonstrated that 100 and 200 ng/ml PEDF downregulated Bcl-2 expression and upregulated Bax protein expression (P<0.05 or P<0.01 vs. control group and H/R group). CONCLUSION: H/R increases VSMC proliferation, whereas PEDF inhibits VSMC proliferation and promotes apoptosis after H/R, possibly through Bcl-2 and Bax pathways.