Platelet rich plasma (PRP) and platelet rich fibrin (PRF) are considered excellent concentrated sources of growth factors (PDGF, TGF-β, VEGF, bFGF) and cytokines fundamental for wound healing. The aim of this study was to evaluate and compare the effect of PRP and PRF on the second intention wound healing through clinical vision, histopathological examination, and changes in interleukin 10 (IL10) and transforming growth factor-β (TGF-β) genes expression. Fifteen adult dogs were used in this study: induction of a 3 cm diameter total thickness cutaneous injury at the right chest region. The animals were divided equally into three groups, and the wounds were treated twice weekly for three successive weeks. The first group (Group A) received only normal saline (control group). The second group was treated by PRP (group B). The third group received PRF treatment (group C). Clinical evaluation, molecular studies of IL10 and TGF-β gene expression, and histopathological examination were used to demonstrate the difference between the three treatment regimens. Results showed a non-significant negative correlation between weight loss and wound healing rate (WHR%), but a significantly high positive correlation between treatment cost either by PRP or PRF with IL10 (0.79*) and WHR% (wound healing rate) (0.994**). The IL10 significantly increased in PRP group, while TGF-b significantly increased in the PRF group. This study concluded that the PRP and PRF exhibited higher regeneration capacity and accelerated the quality of wound healing.