Usually, in clinical practice, only the external characteristics of the forming granulation tissue are evaluated, which is insufficient and can lead to errors in treatment. The morphological characteristics of granulation maturity were evaluated in laboratory models or individuals without carbohydrate metabolism disorders. Methods: The study was conducted in the design of an open prospective, randomized comparative study with parallel groups, including patients with diabetes mellitus and diabetic foot syndrome. General clinical, biochemical, instrumental, functional, morphological, immunological, histochemical, and statistical research methods were carried out. Results: Modern methods of local treatment after primary surgical treatment of chronic wounds should be used differentially depending on the volume of the wound and the amount of exudate. This will significantly improve the therapeutic prognosis and shorten the duration of treatment. The optimization of the treatment process was noted, and the period of stay of the patient in the hospital was significantly reduced. The intensity of reparative processes can be assessed by determining immunohistochemical markers such as CD31, CD68, osteopontin, activity of matrix metalloproteases, and tissue inhibitor of metalloproteases. As a reliable predictor of good wound healing, there is an increase in local microhemodynamics according to transcutaneous oximetry. Conclusions: Reparative processes in the soft tissues of the lower extremities are impaired in individuals with diabetes mellitus. Different types of local treatment of wounds have different effects on the intensity of healing processes in patients with diabetes mellitus. The type of topical treatment may affect local microhemodynamics in the tissues surrounding the wound.