Objective To investigate the CT features and anatomic basis of peritoneal and retroperitoneal spread of primary acute duodenal inflammation. Methods Twenty-six cases of peritoneal and retroperitoneal spreading acute duodenum inflammation confirmed by gastroscopy and clinical diagnosis during January 2010 to December 2014 were collected. Then we analyzed the CT manifestations of their inflammatory features, and abdominal cavity and retroperitoneal diffusion rules. Results According to the inflammation location, in the 26 cases, there were 1 case of inflammation in the descending part of duodenum, 1 in the horizontal part of duodenum, 15 in both the descending and horizontal parts of duodenum, 7 in both the horizontal and ascending parts of duodenum, and 2 in all the descending, horizontal and ascending parts of duodenum. According to the peritoneal and retroperitoneal spreading locations of acute duodenum inflammation, there were 20 cases of transverse mesocolon and mesenteric root swelling, 17 cases of enlargement of the head of pancreas, 6 cases of ascending colon and ileocecal swelling, 5 cases of anterior and posterior renal fascia of right kidney and perinephric fascia of right kidney swelling, 3 cases of effusion between the anterior and posterior renal fascia and lateral cone fascia of right kidney, 1 case of transverse mesocolon, mesenteric root, and the right pelvic swelling, and 1 cases of abdominal pelvic effusion. Conclusions Acute duodenum inflammation is mainly located in the descending and horizontal parts of duodenum. Different duodenal segments have different degrees of inflammation, while the horizontal segment is the most obvious. Inflammation involving two segments and above can be combined with ulcers. The inflammation infiltrates through transverse mesocolon, mesenteric root, anterior and posterior renal fascia of the right kidney, and spreads to the abdominal and retroperitoneal space, which causes the ascending colon and ileocecal swelling. The effusion can be observed in retroperitoneal space, anterior and posterior renal fascia and abdominal cavity.