We have investigated the effect of specific neurokinin-1 receptor (NK1R) antagonist, CP96,345, on the regulation of expression of the adhesion molecules ICAM-1, VCAM-1, E-selectin and P-selectin, as well as leukocyte recruitment during acute pancreatitis (AP). AP was induced in male balb/C mice by 10 consecutive hourly intraperitoneal (i.p.) injections of caerulein. In the treatment groups, CP96,345 was administered at 2.5 mg/kg i.p. either 30 min before or 1 hour after the first caerulein injection. The animals were sacrificed, and the lungs and pancreas were isolated for RNA extraction and RT-PCR, or immunohistochemical (IHC) staining. The mRNA expression of the four adhesion molecules was upregulated in the pancreas during AP. Treatment with CP96,345 effectively reduced the mRNA expression of P-selectin and E-selectin but not ICAM-1 and VCAM-1. In the lung, ICAM-1, E- and P-selectin mRNA expression increased during AP. Antagonist treatment suppressed this elevation. Similar expression pattern was seen in the IHC stainings. Intravital microscopy of pancreatic microcirculation revealed the effect of CP96,345 on leukocyte recruitment. Current study provides important information on the relationship between NK1R activation and the regulation of adhesion molecules. Also, this study points to the differential regulation of inflammation in the pancreas and lung with AP.