Purpose: Hypericin, a specific inhibitor of protein ki-base C, has been reported to have potential as a thera-peutic dru for proliferative vitreoretinopathy (PVR) in vitro and in vivo. In the present strdies, we analyzed the dynamic changesin Ca2+ in flux and freeintracellular Ca2+ concentration Ca2+ of cultured human retinal pigment epith (RPE) cells after stimulation with hypericin in an attempt to elucidate its mechnism as a therapeutic drug for PVR, Methods: RPE cells were plated in a special plastic dish and then stimulated with 100 nM phorbol-12myristate-13-acetate (PMA) and/of 6 hypericin con-centrations (0.5, 1, 2, 3, 4 and 5 μM), after which Ca2+ influx and Ca2+ were determined using the fluores-cence Ca2+ dye fluo-3 AM and laser scanning confocal microscopy. Results: The fluorescence in resting Rpe Cells was strong and distributed throughout the cells. The nucleus appeared more fluorescent than the cyto-plasm. After stimulation with 0.5μM hypoericin, no ob-vious change of Ca2+ influx and Ca2+ was observed. In contrast, stimulation with higher concentrations of hy-pericin (1-5μM) led to a rapid decrease in Ca2+influx and Ca2+ which was significantly different from those de-tected without hypericin (contro experiments). In addl-tion , no significant differences in Ca2+ were found between 1 and 5μM hypericin used. Stimulation with hypericin, which was applled immediately after preincu-bation with PMA for 24 h not further change Ca2+ influx and Ca2+ Conclusion: In Rpe cells, high concen-trations of hypericin (1-5μM) significantiy inhibit Ca2+ influx and induce a decrease in Ca2+. Therefore, hypericin has potential as a therapeutic drug for PVR maybethrough its inhibition of the Ca2+ influx pathway.