Background: Ocular complications associated with diabetes mellitus (DM) are progressive and becoming one of the most important causes of morbidity worldwide. Purpose: To evaluate the protective effect of Polygonatum sibiricum polysaccharide (PSP), an important component of P. sibiricum, on ocular complications in streptozocin (STZ) -induced DM rats. Methods: Sprague Dawley rats were made diabetic with STZ (60 mg, i.v.) and then the rats were treated with PSP 200, 400 and 800 mg.d by gavage for 12 weeks. Results: Biochemical analysis indicated PSP lowered the levels of fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) in blood and elevated the levels of insulin (INS) and C-peptide in plasma of DM rats in a dose–dependent manner. Physical measurements revealed that PSP improved clinical symptom of polydipsia, polyphagia, polyuria and weight loss in DM rats. The content of MDA and activity of SOD in plasma were determined and the data showed PSP suppressed oxidative stress reaction. Lens opacification was observed using slit lamp illumination and the data showed PSP delayed cataract progression in a dose-dependent manner. Electroretinogram showed PSP treatment reversed the decrease of ERG b and OPs2 waves’ amplitudes. Flash-visual evoked potential indicated peak time of P2 wave was prolonged and the amplitude of N2-P2 was lowered in DM group and PSP suppressed these changes. Fundus fluorescein angiography showed PSP alleviated the retinal vasculopathy in a dose–dependent manner. HE staining showed that group DM had thinner retina than the control and PSP intervention increased retinal thickness. FITC-dextran perfusion showed retinal vascular circuity veins became smooth after PSP intervention. TUNEL showed positive nuclei number in the diabetic retinas were significantly higher than the control (P < 0.05).PSP mediated promotion of BCL-2 inhibited retinal VEGF and TGF—β2 and also resulted in a significant decrease in apoptosis.IHC result showed the expression levels of Bax and VEGF BC and lowest in group DM. RT-PCR showed that PSP intervention decreased Bax, EGF, P38, VEGF, and TGF-β mRNA expression and increased Bcl-2 mRNA expression. PSP intervention up-regulated the expression of Bcl-2 proteins and down-regulated the expression of Bax, EGF, P38, VEGF, and TGF-β proteins. All these results followed similar dose-dependent manner. Conlusion: These results suggest that administration of PSP slows the progression of diabetic retinopathy and cataract through alleviating hyperglycemia and reducing oxidative stress in STZ-induced DM rats.