〔Abstract〕 Objective To investigate the effect of capsaicin on retinal vascular permeability in diabetic rats(DM). Methods 24 eight-week-old male sprague-dawley(SD) rats were randomly categorized into four groups(n=6): control group(NC), diabetic group(DM), diabetic group with 3 mg/kg capsaicin treatment(CAP3) and diabetic group with 6 mg/kg capsaicin treatment(CAP6). Type 2 diabetic rat(T2 DM) model was established by high-fat diet combined with small-dose streptozotocin(STZ)induction. The body weight and fasting blood glucose in 4 groups were monitored. Total cholesterol(TC), triglycerides(TG), low density lipoprotein(LDL), high density lipoprotein(HDL) concentrations in serum were detected according to manufacturer′s instructions. Evans blue angiography was used to observe the changes of retinal vascular permeability.Immunofluorescence was used to measure the distribution and expression of transient receptor potential vanillic 1(TRPV1) in retina. Western blot was used to detect the expression of TRPV1, vascular endothelial growth factor(VEGF) and occludin in rat retina. Results Compared with the DM group, serum total cholesterol(TC), triglyceride(TG) and low density lipoprotein(LDL) levels in the CAP3 and CAP6 groups significantly decreased(P<0.01). The results of angiography showed that the retinal vascular permeability increased in the DM group and that there were many strong fluorescent leakage areas, while the leakage was reduced in CAP3 and CAP6 groups. In CAP3 and CAP6 groups, immunofluorescence showed the activation of TRPV1 in the retinal ganglion cell layer, inner nuclear layer and outer nuclear layer. Western blot indicated that the expression of TRPV1 and occludin increased while the expression of VEGF decreased(P<0.01). Conclusion Capsaicin may exert the effect of improving diabetic retinopathy, underlying which the mechanism may be that capscicin activates retinal TRPV1, resulting in the downregulation of VEGF and upregulation of occuldin.