Objective To investigate the ameliorative effect and possible mechanism of Danshensu in retinal vein occlusion (RVO) rats. Methods Eight SPF grade male SD rats were randomly selected as the control group. The RVO model was induced by Bengal red combined with the laser photodynamic method in the left eye of the remaining rats. The model rats were randomly divided into model, Danshensu low (15 mg/ kg), medium (30 mg/ kg), and high dose group(60 mg/ kg), with eight rats in each group. Rats in control and model groups were injected with the same amount of normal saline through the caudal vein every day for 21 days. Fundus fluorescein angiography was used to observe the retinal vein structure. The venous blood flow velocity was measured by ear vein microcirculation. A full field electroretinogram(ffERG) was used to evaluate retinal functions. The retinal layer thickness was measured by optical coherence tomography. Histological changes of the retina were observed by HE staining. The relative expression of VEGF mRNA was measured by RT-qPCR. Expression of hypoxia inducible factor 1α (HIF1α), extracellular signal regulated kinase 1/2 (ERK1/2), p-ERK1/2, focal adhesion kinase (FAK), p-FAK, VEGF, and pigment epithelium-derived factor (PEDF) in retinal tissue was detected by Western blot. Results Before administration, compared with the control group, the retinal vein blood flow of model rats was interrupted, distal blood vessels were tortuous and dilated, the retinal thickness was increased, the amplitudes of ffERG a and b waves were decreased, and the blood flow velocity of the ear vein was decreased (P<0. 05). After administration, compared with the control group, retinal vein occlusion was recanalized, the retinal thickness, amplitudes of ffERG a and b waves, and blood flow velocity of the auricular vein were decreased (P<0. 05), and the retina was damaged by various degrees. The retinal structure of the model group was incomplete, the number of ganglion cell layer cells was decreased, the photoreceptor cell layer of the outer nuclear layer was almost lost, and relative expression of VEGF mRNA and HIF1α, p-ERK1/2, and p-FAK proteins was increased in retinal tissue, while the relative expression of PEDF protein was decreased (P<0. 05). Compared with the model group, the changes in the above indexes and factors in the three Danshensu treatment groups were reversed (P<0. 05) and pathological damage of the retina was gradually reduced. The effect of Danshensu was dependent on dose (P<0. 05). Conclusions Danshensu reduces retinal tissue injury, promotes recovery of blocked venous microcirculation, and improves retinal functions in RVO rats. Its mechanism may be related to inhibiting activation of VEGF-related angiogenesis pathways.