The long-term effects of octreotide, the synthetic analog of the hormone somatostatin, on acute experimental pancreatitis were studied. Acute pancreatitis was induced in rats by intraparenchymal injections of 0.5 ml 5% or 10% sodium taurocholate. Octreotide (10 mg/kg/day, subcutaneously), or saline injections as controls, were started four hours later, and their effects were assessed 30, 60, and 90 days after the induction of pancreatitis. Neither intrapancreatic saline injections nor octreotide administration without the induction of pancreatitis caused any biochemical or histological abnormalities. Taurocholate-induced pancreatitis was followed by remarkable hyperglycemia, which was ameliorated by octreotide. Thirty days after induction of pancreatitis, glucose levels were 269+/-21 mg/100 ml and 153+/-17 mg/100 ml in the control and octreotide treated animals, respectively (P < 0.02). Octreotide administration was associated with increased pH values after 60 and 90 days (P < 0.05 for the 90 days group). The levels of hematocrit, calcium, and amylase were already within the normal ranges after 30 days and were unaffected by octreotide. There were no signs of chronic exocrine insufficiency and all the surviving rats gained weight during the follow-up. However, the relative weights of the pancreases of the octreotide-treated animals were higher than those of the controls 30 days after IOP. Histopathological evaluation demonstrated regeneration of the pancreatic tissue, and increased number and hypertrophy of the islets of Langherhans. There were no significant differences whether the octreotide treatment was given for only 48 or 96 hr. Survival was significantly improved by octreotide; only one octreotide-treated rat (2.5%) with 10% taurocholate-induced pancreatitis died, while six (15%) of the control animals succumbed (P < 0.05). These studies provided data on the sequelae of acute pancreatitis and showed that octreotide may have long-term beneficial effects in this disease.