AIM: To study the effects of Tetramethylpyrazine (TMP) on retinal pigment epithelium (RPE) degeneration, choroidal blood flow and oxidative stress of RPE cells. METHODS: The 35mg/kg NaIO3-induced RPE degeneration rat eyes was given 25μg 1% TMP eye drops 3 times a day for 7 days before NaIO3 injection, and then 2 to 4 weeks after NaIO3 injection. RPE function was measured with c-wave of electroretinogram (ERG). Colored microsphere technique was used for in vivo experiments to determine the choroidal blood flow in ocular hypertensive (40mmHg) rabbit eyes. Methylthiazoltetrazolium (MTT) assay was used to study in vitro effect of TMP on various oxidants induced injury in the hRPE (ARPE-19 (ATCC, Manassas, VA, USA)) . RESULTS: Two weeks after NaIO3 injection, the amplitude of ERG c-wave fell markedly in NaIO3 group to 36% of control group(P <0.01). No apparent difference was observed in TMP+NaIO3 group. Four weeks later, the NaIO3 group fell to 46% of control group (P<0.01), while the TMP+NaIO3 group fell to only 77% of control group (P<0.01). There was a 67% reversal of the ERG c-wave by TMP as compared to NaIO3 group(P<0.01). The choroidal blood flow was significantly increased at all time points (at 30, 60 and 120 minutes after TMP instillation) as compared with corresponding controls. TMP had no effect on hypoxia-(1%O2), t-BHP- and H2O2-induced damage in RPE cells. 10(g/mL TMP could reverse 1 and 3mM NaN3-induced loss of viability of RPE by 18.5% (P <0.01) and 23% (P<0.01), respectively. 30μg/mL TMP could reverse 30 and 100mM NaIO3 induced loss of viability of RPE by 18.1% (P <0.05) and 16.8% (P <0.01), respectively. CONCLUSION: TMP can significantly protect RPE from NaIO3 induced degeneration in vivo and oxidative stress in vitro and can increase choroidal blood flow markedly in vivo.