The aim of this study was to investigate whether IV secretin administration is useful to enhance the delineation of the main pancreatic duct (MPD) and its side branches, and if it provides additional information concerning signal voids and strictures. Twenty-seven patients referred for abdominal pain or laboratory abnormalities (group 1, n = 13) or for the follow-up of chronic pancreatitis (CP; group 2, n = 14) were studied. Magnetic resonance cholangiopancreatography was acquired at 1.5 T before and after IV secretin by a coronal 3D TSE T2-weighted sequence with maximum intensity projection postprocessing. In group 1 secretin provided a better visualization of MPD in 9 patients. In a patient with pancreas divisum, it allowed suggestion of stenosis of the accessory papilla, confirmed at endoscopic retrograde cholangiopancreatography (ERCP). In group 2 secretin provided a better visualization of MPD only in the 3 patients with mild disease. A mild dilation upstream a stricture occurred in 2 cases and a marked dilation appeared upstream a wallstent which was non-patent at ERCP. Few changes were noticed concerning side branches. These preliminary results indicate that in patients without CP, secretin improves MPD delineation avoiding invasive diagnostic ERCP. In patients with mild CP secretin does not improve the characterization of signal voids, but it may be useful to appreciate their significance and to follow-up stenosis.