Objective  To study the effect of sulodexide on the repair of diabetic retinopathy and the regulation of MAPK pathway in rats.    Methods  Totally 72 rats were randomly divided into normal control group, diabetic retinopathy group, low, middle and high dose of sulodexide group and metformin hydrochloride group. Except normal control group, other rats were intraperitoneally injected with streptozotocin to establish the rat model of diabetic retinopathy. Rats in the low, middle and high dose sulodexide groups were given sulodexide by intragastric administration of 10 mg/kg，20 mg/kg and 40 mg/kg, respectively. Metformin hydrochloride group was given metformin hydrochloride of 200 mg/kg, once a day for 12 weeks. The levels of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c) and serum levels of advanced glycation end products (AGEs), interleukin-6 (IL-6), IL-1β, and levels of glucose transporter 1 (GLUT-1), glucose transporter 3(GLUT-3), superoxide dismutase (SOD) and malondialdehyde (MDA) in retina were detected. The levels of p38 MAPK and phosphorylated p38 MAPK (p-p38 MAPK) in retina were detected by immunohistochemistry and Western blotting. Retinal pathological changes and ganglion cell count were examined by HE staining.    Results The levels of FBG and HbA1c, serum AGEs, IL-6, IL-1 β, GLUT-1, GLUT-3, MDA and p38 MAPK mRNA, p38 MAPK, p-p38 MAPK/p38 MAPK and immunohistochemical integral optical density of retina in sulodexide group were significantly lower than those in diabetic retinopathy group (P<0.05), while the SOD level and ganglion cell number in retinal tissue were significantly higher than those in diabetic retinopathy group (P<0.05).    Conclusion  Sulodexide can regulate blood glucose level and retinal glucose metabolism in diabetic retinopathy rats, and repair retinal pathological damage, and its mechanism may be related to the regulation of MAPK pathway.