Pancreatitis is thought to be triggered by the inappropriate activation of digestive enzymes. Experimental evidence suggests that while enzyme activation may be the initiating event, it but does not determine the progression of the disease. We hypothesized that the intensity of the inflammatory response is the determining factor for pancreatitis severity. The recruitment of leukocytes to the site of inflammation is dependent on cellular adhesion molecules (CAMs) which regulate leukocyte migration through the endothelium. The expression of CAMs was evaluated in cerulein induced pancreatitis, a model of mild self limiting pancreatitis that mimics edematous pancreatitis in human. Adult mice received hourly subcutaneous injection of 25 μg/kg cerulein or placebo, for a total of 5 doses. Animals were sacrificed at time 0, 1, 3, 6, 9, 12, and 24 h. PECAM-1, ICAM-1, and P-Selectin mRNAs were assayed by in situ hybridization on pancreas sections. Five animals were studied at each time point. PECAM-1 mRNA was easily detected in the endothelium of small and large vessels of the pancreas but the expression was not affected by the treatment. ICAM-1 mRNA was not detected in controls or treated animals. P-Selectin mRNA was also not detected in control animals nor in cerulein treated mice at times 0, 1 and 3 h. However, at the 6 h time point, abundant transcripts were seen on the endothelium of almost all small and large vessels. This increased expression was still apparent at 9 h, but decrease thereafter. In conclusion, cerulein induced pancreatitis was associated with a transient but important increase in P-Selectin mRNA. This increased expression preceded the maximal leukocyte infiltration and tissue damage seen at 12 h, strongly suggesting that P-Selectin plays an active role in the progression of the disease.