BACKGROUND: Bacterial infections and impaired angiogenesis have been obstacles to diabetic wound healing, and the problem of multidrug resistance cannot be ignored, so there is an urgent need to find a new therapeutic strategy. OBJECTIVE: To prepare platelet-camouflaged silver nanoparticle hydrogel and observe its therapeutic effect on diabetic wounds. METHODS: (1) In vitro test: The ultra-small silver nanoparticles (usAgNPs) were obtained by reflux heating. usAgNPs-PL/CMC hydrogel was prepared by coupling it with platelets (PL) and adding it to the carboxymethyl cellulose (CMC) hydrogel. The microstructures, swelling properties, and mechanical properties of the hydrogel were characterized. The antibacterial activity of the hydrogel was tested by 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)5[(phenylamino)carbonyl]- 2H-tetrazolium hydroxide method, reactive oxygen species method, bacterial biofilm method, and bacterial activity. (2) In vivo test: Forty SD rats were randomly divided into sham operation group, model group, CMC hydrogel group, usAgNPs/CMC hydrogel group, and usAgNPs-PL/CMC hydrogel group, with eight rats in each group. The type 1 diabetes model was established in the other four groups except the sham operation group. After successful model establishment, a skin wound (20 mm in diameter) deep to the fascia layer was made on the back of rats of the five groups. Rats in the sham operation group and model group were injected with normal saline. The rats in the CMC hydrogel group, usAgNPs/CMC hydrogel group, and usAgNPs-PL/CMC hydrogel group were implanted with the corresponding hydrogel, separately. The wound healing condition and healing quality were observed after 14 days of treatment. RESULTS AND CONCLUSION: (1) In vitro test: The usAgNPs-PL/CMC hydrogel had a uniform three-dimensional network structure, good mechanical properties, and strong water absorption ability, which could remarkably inhibit the growth of Escherichia coli and Staphylococcus aureus, and had a good inhibition and clearance effect on the formation of biofilms of the two bacteria, and had a good antibacterial ability. (2) In vivo test: After 14 days of treatment, the wounds of the usAgNPs-PL/CMC hydrogel group were basically closed. The wound healing rate was the highest, and the number of wound colonies was significantly lower than that of the model group. After 14 days of treatment, hematoxylin-eosin and Masson staining showed that the tissue structure of regenerated dermis appeared on the wounds of the usAgNPs-PL/CMC hydrogel group, usAgNPs/CMC hydrogel group, and CMC hydrogel group, and the epidermis of the new granulation tissue was complete and thick. Parallel mature collagen fibers were observed in the usAgNPs-PL/CMC hydrogel group. After 7 days of treatment, CD31 immunohistochemistry and Ki67 immunofluorescence staining showed that the usAgNPs-PL/CMC hydrogel group had the highest number of microvessels and fibroblasts. (3) The results showed that usAgNPs-PL/CMC hydrogel could accelerate wound healing in type 1 diabetic rats by rapidly inhibiting bacteria and promoting angiogenesis. [ABSTRACT FROM AUTHOR]