The aim was to use immunohistochemistry to assess the dynamics of p53, casp3, and bcl-2 protein expression in rat skin connective tissue cells during the stages of post-traumatic histogenesis. Material and methods. The experiment was performed on male Wistar rats (n=40) weighing 200–230 g. A deep transverse incisional skin wound was created in the middle third of the thigh using a sharp scalpel. Specimens were obtained at 12 hours, 24 hours, 2, 3, 6, 10, 15, and 25 days following injury, using 5 animals for each time interval. Five intact animals served as controls. Expression of p53, caspase-3, and bcl-2 was assessed immunohistochemically. Data analysis employed parametric statistical approaches. Results. When mechanical damage occurs in skin connective tissues – comprising both loose and dense irregular connective tissue of the dermis and hypo- dermis, along with hypodermal adipose tissue – this induces predictable histogenetic processes in the perine- crotic wound region, including programmed cell death activation. Key findings revealed distinct patterns of p53, casp3, and bcl-2 protein expression. The study demonstrated distinct expression patterns of apoptotic markers proteins during both: the necrotic and inflammatory phases of wound healing, and the proliferative, differentiation, and adaptive phases of regenerative histogenesis. Conclusion. The proportion of p53-, casp3-, and bcl-2- positive cells varied significantly across different wound healing phases. Maximal Casp3+ cell counts occurred at two time points: during the acute inflammatory phase (day 2) and subsequently during tissue differentiation (day 10). Peak p53+ cell counts were observed at three time points: during acute inflammation (24 h and day 3), and later during regenerative histogenesis (day 15). Significant peaks in Bcl-2 immunopositive cells were detected at three time points: 24 hours, 6 days, and 15 days following trauma.