AIM: To clarify the innervation of the antro-pyloric region in humans from a clinico-anatomical perspective. METHODS: The stomach, duodenum and surrounding structures were dissected in 10 cadavers, and immersed in a 10mg/L solution of alizarin red S in ethanol to stain the peripheral nerves. The distribution details were studied to confirm innervations in the above areas using a binocular microscope. Similarly, innervations in 10 Suncus murinus were examined using the method of whole-mount immunohistochemistry. RESULTS: The innervation of the pyloric region in humans involved three routes: One arose from the anterior hepatic plexus via the route of the suprapyloric/ supraduodenal branch of the right gastric artery; the second arose from the anterior and posterior gastric divisions, and the third originated from the posterior-lower region of the pyloric region, which passed via the infrapyloric artery or retroduodenal branches and was related to the gastroduodenal artery and right gastroepiploic artery. For Suncus murinus, results similar to those in humans were observed. CONCLUSION: There are three routes of innervation of the pyloric region in humans, wherein the route of the right gastric artery is most important for preserving pyloric region innervation. Function will be preserved by more than 80% by preserving the artery in pylorus-preserving pancreaticoduodenectomy (PPPD). However, the route of the infrapyloric artery should not be disregarded. This route is related to several arteries (the right gastroepiploic and gastroduodenal arteries), and the preserving of these arteries is advantageous for preserving pyloric innervation in PPPD. Concurrently, the nerves of Latarjet also play an important role in maintaining innervation of the antro-pyloric region in PPPD. This is why pyloric function is not damaged in some patients when the right gastric artery is dissected or damaged in PPPD. METHODS: The stomach, duodenum and surrounding structures were dissected in 10 cadavers, and immersed in a 10 mg / L solution of alizarin red S in ethanol Also, innervations in 10 Suncus murinus were examined using the method of whole-mount immunohistochemistry. RESULTS: The innervation of the pyloric region in humans involved three routes: One arose from the anterior hepatic plexus via the route of the suprapyloric / supraduodenal branch of the right gastric artery; the second arose from the anterior and posterior gastric divisions, and the third originated from the posterior-lower region of the pyloric region, which passed via the infrapyloric artery or retroduodenal branches and was related to the gastroduodenal artery and right gastr For Suncus murinus, results similar to those in humans were observed. CONCLUSION: There are three routes of innervation of the pyloric region in humans, where the route of the right gastric artery is most important for preserving pyloric region innervation. Function will be preserved by more than 80% by preserving the artery in pylorus-preserving pancreaticoduodenectomy (PPPD). However, the route of the infrapyloric artery should not be disregarded. This route is related to several arteries (the right gastroepiploic and gastroduodenal arteries), and the preserving of these arteries is advantageous for preserving pyloric innervation in PPPD. Concurrently, the nerves of Latarjet also play an important role in maintaining innervation of the antro-pyloric region in PPPD. This is why pyloric function is not damaged in some patients when the right gastric artery is dissected or damaged in PPPD.