The diabetic foot ulcer (DFU) are serious problems to diabetes and may be associated with late healing and septic manifestation, consequently result in amputation which is an extortionate incident. The innate repair receptor (IRR) is expressed by injured tissues and is activated by erythropoietin produced and released into damaged tissue. Activation of the IRR might provide benefit for diabetic wound healing. This study evaluated effect of a specific IRR agonist, ARA290, on skin wound repair. The aim of the present study was to evaluate the effect of topical application based on ARA290, in streptozotocin-induced diabetic incision wound models rats. The treatment was performed daily, until day 14 after wound induction. Wound closure was determined and the features of the repaired tissue were examined, including amount of collagen and protein content, biochemical parameters, antioxidant status and proinflammatory cytokines. The data confirmed wound healing activities via macroscopic, biochemical, immunofluorescent and molecular methods. There was meaningful acceleration in wound closure rate, decrease in the period of re-epitalization, greater amount of collagen and protein content in ARA290 treated group when compared with control group. The increase of serum insulin and HDL was divergent with blood glucose decrease and reduced lipid level. The healing effect was confirmed by reduced levels of inflammatory cytokines and lipid peroxidation and augmented antioxidants. The results propose that ARA290-arbitrated IRR activation may signify an appealing approach to treat diabetes-associated wound healing.