Objective To establish a rabbit model of diabetic skin-muscle defect and evaluate the effects of platelet-rich fibrin (PRF) on diabetic wound cavities, thereby providing a theoretical basis for the clinical application of PRF in improving the healing of diabetic wound cavity.MethodsA total of 51 New Zealand white rabbits were randomly divided into 2 groups: the blank control group (17 rabbits) and the diabetic group (34 rabbits). The diabetic group firstly underwent induction of diabetes. 7 days after successful induction, a skin-muscle defect model was created on both lateral thighs of each rabbit. The diabetes group was then further randomized into a diabetic control group and a PRF experimental group. Each group contained 34 wounds. After skin-fascia-muscle fixation was performed, autologous PRF was implanted into the PRF experimental group, while normal saline was injected into the other two groups. All rabbits were housed individually under the same conditions postoperatively, with regular dressing changes. The healing of the wound cavity was monitored and assessed. On the 12th postoperative day, the rabbits were euthanized. Wound-cavity tissue growth rate and wound-healing rate were measured, and specimens were collected for hematoxylin-eosin staining, Masson’s trichrome staining, and CD34 immunohistochemical staining for histological analysis.Results The PRF experimental group showed the best healing, with the highest tissue growth in the wound cavity and the highest wound healing rate, followed by the the blank control group, and the diabetic control group showed the poorest results. The tissue growth rate in the wound cavity was: PRF experimental group (91.33±4.63)% > the blank control group (83.41±5.54)% > the diabetic control group (72.91±5.17)%, with statistically significant differences among groups (P<0.05). The wound healing rate was: PRF experimental group (83.85±4.95)% > the blank control group (80.93±3.46)% > the diabetic control group (71.05±2.98%), with statistically significant differences among groups (P<0.05). HE staining revealed fewer inflammatory cells and more neocapillaries in the PRF experimental group. Masson’s trichrome staining demonstrated greater collagen content, thicker fibers, and more orderly fiber arrangement with PRF. CD34 staining showed microvessel densities:PRF experimental group(18.57±3.67) > the blank control group (13.36±2.43) > the diabetic control group (10.54±1.37 ) (vessels/mm2) (P<0.05). Conclusion PRF promotes the growth of granulation tissue within diabetic composite tissue defects, facilitating cavity closure and accelerating wound healing