To investigate the effects of Scrophulariae Radix extract on the damage of human retinal microvascular endothelial cells(HRMECs) in diabetic retinopathy(DR) and decipher the underlying mechanism.Methods:The simple random method was adopted to group HRMECs：control，model(30 mmol/L glucose)，observation(30 mmol/L glucose+100 μg/mL Scrophulariae Radix extract)，model+anti-NC(transfected with anti-NC+30 mmol/L glucose)，and model+anti-miR-646(transfected with anti-miR-646+30 mmol/L glucose).Thirty mice were assigned into control，model(60 mg/kg streptozotocin)，and observation(60 mg/kg streptozotocin+100 mg/kg Scrophularia Radix extract) groups(n=10) according to the simple random method.Cell proliferation，migration，and expression of miR-646，vascular endothelial growth factor A(VEGFA)，intercellular adhesion molecule-1(ICAM-1)，and platelet endothelial cell adhesion molecule-1(CD31) were compared among different cell groups.In addition，the expression of ICAM-1 and CD31 in the retinal tissue and the degree of retinal edema were compared among different mouse groups.Results:In the cell experiment，compared with control group，the model group presented upregulated expression of miR-646 and ICAM-1 and downregulated expression of VEGFA and CD31(all P<0.05).Compared with the model group，the observation group exhibited downregulated expression of miR-646 and ICAM-1 and upregulated expression of VEGFA and CD31(all P<0.05).Compared with the model+anti-NC group，the model+anti-miR-646 group showcased increased cell proliferation rate，migrated cells，and VEGFA expression，downregulated miR-646 expression，and decreased apoptosis rate(all P<0.05).In the animal experiment，compared with the control group，the model group showcased upregulated expression of miR-646 and ICAM-1，downregulated expression of VEGFA and CD31 in the retinal tissue(all P<0.05)，and aggravated retinal edema.Compared with model group，the observation group demonstrated downregulated expression of miR-646 and ICAM-1，upregulated expression of VEGFA and CD31 in the retinal tissue(all P<0.05)，and relieved retinal edema.Conclusion:Scrophulariae Radix extract may regulate the proliferation，migration，and apoptosis of HRMECs via miR-646/VEGFA to promote the remission of retinal edema in diabetic retinopathy.