Objective: To investigate the therapeutic effect of rutecarpine on rats with severe acute pancreatitis (SAP) and its mechanism. Methods: Fifty SD rats were equally randomized into sham operation group and 4 experimental groups. Rats in experimental groups underwent retrograde cholangiopancreatic duct injection of 5% sodium taurocholate to induce SAP model, and then were given the treatment with normal saline, ulinastatin, rutecarpine, or ulinastatin plus rutecarpine, respectively. Twenty-four hours after operation in each group, the pathological examination was performed, the serum amylase activity was measured, and the levels of endothelin 1 (ET-1) and calcitonin gene related peptide (CGRP) in the plasma and pancreatic tissue were determined. Results: Except in sham operation group, all the experimental groups exhibited the pathological profiles of pancreatitis of varying degrees in the pancreatic tissue. Compared with sham operation group, the serum amylase activity, and levels of ET-1 in the plasma and pancreatic tissue in all experimental groups were increased with different degrees, while the contents of CGRP in plasma and pancreatic tissue were significantly increased in rutecarpine treatment group and combination treatment group (all P<0.05), and showed no obvious change in the remaining experimental groups (all P>0.05). Among experimental groups, the pancreatic damage was less severe, and serum amylase activity as well as the levels of ET-1 in plasma and pancreatic tissue were significantly decreased in the groups that received drug treatment, especially combination drug treatment, compared with the model group treated with saline (all P<0.05). Conclusion: Rutecarpine has protective effect against SAP in rats, which may be associated with its increasing CGRP level and thereby improving the microcirculation of pancreatic tissue.