AIM:To determine whether hydroxysafflor yellow A(HSYA) inhibits high glucose-induced cell proliferation and expression of vascular endothelial growth factor(VEGF) mRNA in retinal capillary endothelial cells(Macaca rhesus monkey vascular endothelial cells,RF/6A cells).METHODS:RF/6A cells cultured in vitro were divided into NG+H0 group in which contained with normal glucose of 5.5mol/L,and was added with HSYA of 0mg/L,and were divided into HG+H0,HG+H18,HG+H37,HG+H73 group,in which contained with high glucose of 22mmol/L and were added with HSYA of 0,18,37 and 73mg/L,respectively.At 24,48,72 hours cultured,the cells were observed by inverted microscope.The effects of HSYA on cell proliferation and expression of VEGF mRNA were tested by MTT assay and RT-PCR(reverse transcription-polymerase chain reaction),respectively.RESULTS:The results of MTT assay for the effects of HSYA on the proliferation of RF/6A cells were showed as follows:at 48hours of cells cultivation,compared with HG+H0,the effects in HG+H37 and HG+H73 group were statistically significant(P<0.01).With the concentration of HSYA increased in high glucose groups,the absorbance values of RF/6A cells showed a descending trend.At 72hours of cells cultivation,there were statistically significant effects in groups of HG+H18,HG+H37 and HG+H73 when compared with HG+H0 group(P<0.01).With the concentration of HSYA increased in high glucose groups,the absorbance values of RF/6A cells showed a descending trend,and there was a marked reduction in HG+H73 group compared with the HG+H18 and HG+H37 group(P<0.01,P<0.05,respectively).The RT-PCR results for the effects of HSYA on VEGF mRNA expression were showed as follows:at 48hours of cells cultivation,the expression of VEGF mRNA in HG+H37,HG+H73 group was statistically significant lower than that in HG+H0 group(P<0.01) and with the same results showed in HG+H18,HG+H37,HG+H73 group at 72hours of cells cultivation(P<0.01).CONCLUSION:These results suggested that HSYA can inhibit the expression of VEGF and the high glucose-induced proliferation of RF/6A cells.The inhibitory effect of cell proliferation was increased in both time-dependent and dose-dependent manner.These effects may be associated with down-regulating the expression of VEGF mRNA by HSYA.