Objective To study the influence of hyperlipemia on rats with acute pancreatits during pregnancy and its mechanism. Methods Seventy two pregnant Sprague-Dawley rats were randomly divided into the test group and the control group, and then they were fed with high fat diet and balanced diet for 16 days separately. Pregnant rats were given intraperitoneal injection with L-arginine for 2 times (one time is 250 mg/100 g, the other is 200 mg/100 g) at an interval of 1 h. The serum triglyceride (TG), serum amylase (AMS), and lipase (LPS) from blood samples were tested just after injection, and 12 h, 18 h, 24 h, 30 h and 48 h after injection respectively, and wet/dry ratio of pancreas were measured. The histopathological score of pancreatic tissue was evaluated based on microscopic changes, and the expression of TNF-α protein was determined by SP immunohistochemical technique. Results After the last injection, the level of TG in the test group was obviously higher than that in the control group in each time (P<0.05). The peak values of AMS and LPS in the test group appeared at 24, 18 h respectively, while the peaks appeared at 30, 24 h in the control group, respectively, which were significantly lower than those in the test group (P<0.05). Compared with the control group, the wet/dry ratio of pancreas in the test group increased at 12, 18 and 24 h after injection (P<0.05); The pathological changes of pancreas in test group was more serious with higher histopathological score at 0, 12, 18 and 24 h (P<0.05), and expression of the TNF-α protein was higher at 12, 18 and 24 h (P<0.05), too. Conclusion Hyperlipemia can make L-arginine-induced-acute-pancreatitis during pregnancy earlier occur and lead to more serious injury in pancreas. This study demonstrates that hyperlipemia may be a high risk factor for acute pancreatitis during pregnancy, making a great amount of free fatty acid released from TG and up-regulated the expression of TNF-α.