Diabetes mellitus is a chronic condition that causes several complications. Studies indicate that around 1/3 of the diabetic patients in USA suffer cutaneous complications, resulting in a higher morbidity and mortality. In the last years, scientific studies have used the active principle of the natural products to treat acute and chronic wounds. As an example we have the caffeic acid phenethyl ester (CAPE), one of the propolis active principles, that presents potent antioxidant and anti‐inflammatory action. Due the great performance of CAPE to improve the burn healing in rats, as observed in our laboratory, we seek to investigate if this agent can also be beneficial in wound healing of chronic lesions. Diabetes was induced in Swiss mice (males) by multiple streptozotocin injections. After one week, hyperglycemia was confirmed and two excisional wounds (8 mm2 each) were made on the dorsum of these animals (day 0). Mice were divided in two groups, the diabetic mice group (DB group), that received only the vehicle and the diabetic mice CAPE treated‐ group (DB+CAPE group), that received 10μM of CAPE dissolved in the vehicle. The treatment started on the day of the wounds creation and extended until the day of euthanasia, 12 days after wounding, when the wounds were collected. CAPE treatment improved wound inflammatory and oxidative profile; in this group the tumor necrosis factor α (TNF‐α) and phosphorylated nuclear factor kappa B (NFkBp65) protein, nitric oxide synthase 2 (NOS2) and cyclooxygenase‐2 (COX‐2) expression was reduced. These results reflected in the inflammatory cell infiltrate, which was reduced. The reduction in inflammatory cell amount in DC+CAPE group influenced the reduction of the protein carbonylation and lipid peroxidation. In DB+CAPE group, the granulation tissue presented a greater collagen fiber density, with more collagen type I. The improvement in inflammatory parameters influenced the macroscopic parameters. The DB+CAPE group presented a strong tendency towards greater contraction and reepithelization when compared to DB group. These results lead us to believe that the treatment of diabetic lesions with CAPE may be a good option for a therapeutic treatment, with the benefit of being a product of natural origin, which could reduce side effects.Support or Funding InformationFundação de Amparo à Pesquisa do Estado do Rio de Janeiro ‐ FAPERJThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.