AIM:To study the effects of Tetramethylpyrazine （TMP） on retinal pigment epithelium（RPE） degeneration,choroidal blood flow and oxidative stress of RPE cells. METHODS:The35mg/kg NalO₃-induced RPE degeneration rat eyes was given 25μg 1%TMP eye drops 3 times a day for 7 days before NalO₃ injection,and then 2 to 4 weeks after NalO₃ injection.RPE function was measured with cwave 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 NalO₃ injection,the amplitude of ERG c-wave fell markedly in NalO₃ group to 36%of control group（P<0.01）.No apparent difference was observed in TMP + NalO₃ group.Four weeks later,the NalO₃ group fell to 46%of control group（P<0.01）,while the TMP + NalO₃ 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 NalO₃ 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.10μg/mL TMP could reverse 1 and 3mmol/L 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 100mmol/L NalO₃ 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 NalO₃ induced degeneration in vivo and oxidative stress in vitro and can increase choroidal blood flow markedly in vivo.