Background: Random-pattern skin flaps are often utilized to cover numerous skin defects that can occur for a variety of causes, although tissue ischemia is the most prevalent consequence that leads to surgery failure. Protein Kinase D1 (PKD1), a calcium/calmodulin-dependent serine/threonine kinase, has been linked to angiogenesis and has been shown to protect against ischemic cardiovascular disease in several studies. However, no relevant studies on skin flaps have been recorded. Methods: Sixty male Sprague-Dawley rats were randomly separated into control, PKD1, and CID755673 group. We observed postoperative survival, laser Doppler and lead oxide/gelatin angiography were used to assess blood flow, HE (hematoxylin and eosin) staining was used to observe neovascularization, and determined the level of related protein expression through Immunoblotting and immunohistochemistry. Results: The PKD1 group has the largest survival area and the most abundant blood supply. The level of angiogenesis and oxidative stress is the highest, and the level of apoptosis is the lowest. The CID755673 group is the opposite. Conclusion: The findings show that PKD1 increases the flap’s survival rate and is linked to increased angiogenesis, reduced oxidative stress, and apoptosis inhibition.