AIM: To explore whether resveratrol (Res) can inhibit human retinal pigment epithelial cell (ARPE-19 cell) proliferation and migration, and to research the molecular mechanisms. METHODS: ARPE-19 cells were pretreated with various concentrations at 0, 50, 100, 150, 200 and 300 μmol/L of Res, and with 0 μmol/L Res as the control for 24, 48 and 72h. The cell proliferation, apoptosis and migration were measured with cell counting kit-8 (CCK-8), flow cytometry, and wound-healing and Transwell assays, respectively. The expression of proliferating cell nuclear antigen (PCNA), P21 and P27, as well as matrix metalloproteinase-9 (MMP-9) and p38 mitogen-activated protein kinases (p38MAPK) was identified by Western blot. RESULTS: Cell proliferation was effectively inhibited by Res (P<0.05). When pretreated with Res, cells arrested in S-phase increased remarkably (P<0.05), but the apoptosis ratios showed no significant difference between the treatment and control groups (P>0.05). Cell migration was suppressed by Res both in wound-healing assay and Transwell migration assay (P<0.05). Decreases of PCNA, MMP-9 and p38MAPK, as well as increases of P21 and P27 were detected by Western blot (P<0.05). CONCLUSION: Res can inhibit APRE-19 cell proliferation and migration in a concentration-dependent manner with up-regulation of the expression of P21 and P27, and down-regulation of PCNA, MMP-9 and p38MAPK.