Background: Wound healing is a complex process, relates to wound care methods, wound dressing materials, to wound closure according to the reconstruction ladder. Research on dressing materials for full-thickness wounds is increasingly diverse, from herbs, medicinal active ingredients, to tissue engineering. Platelet-rich fibrin (PRF) as a second generation of platelet derivatives, plays an important role in inflammatory, proliferative, remodeling processes in wound healing. Simvastatin, an anti-hyperlipidemic drug, in its development has a pleiotropic effect, can reduce inflammation, increase proliferation, thereby accelerating wound healing by increasing angiogenesis. This study aims to compare the effectiveness of Simvastatin gel 2.5% with Platelet-rich fibrin (PRF) against angiogenesis, fibroblast proliferation, collagen fiber density, and epithelialization rate. Methods: Thirty six rats were randomly divided into three groups. A 2x2 cm full-thickness wound was made on the back of the Winstar mouse. Group A was a control group, the wounds were applied with Carboxymethylcellulose (CMC gel). In group B, the wound was treated with Platelet-rich fibrin (PRF), and in group C, the wound was given Simvastatin gel with 2.5% concentrate. The wounds in each group were dressed with a dressing. Furthermore, the rats were sacrificed on the 3rd and 7th day after treatment, and the samples were taken. Result. There was a significant difference (p <0.05), which showed better effectiveness in angiogenesis, fibroblast proliferation, and epithelialization rate of wounds treated with Simvastatin gel 2,5%. Conclusion: Simvastatin gel with a concentrate of 2.5% accelerates wound healing, but still requires further research, especially the right concentration so that it can be applied properly in humans.