We studied the effect of oral zinc administration on functional and morphological regeneration of the remnant pancreas after 80% pancreatectomy in dogs. After 80% pancreatectomy, both endo- and exocrine function (assessed by the sum of plasma immunoreactive insulin on the intravenous glucose tolerance test and amylase output on the cerulein-secretin test) markedly deteriorated, the pancreatic regeneration rate (change in weight of the remnant pancreas between the time of surgery and autopsy) was very poor, and the zinc concentration in pancreatic tissue decreased in dogs fed the standard diet. In dogs fed the high-zinc diet, pancreatic function and regeneration rate were significantly improved, and the zinc concentration in pancreatic tissue was maintained. Early cell proliferation (assessed by ornithine decarboxylase activity, DNA synthesis, and proliferating cell nuclear antigen labeling index in the remnant pancreas) after pancreatectomy was significantly enhanced in the high-zinc diet group compared to the standard diet group. Correlation analyses between parameters of early cell proliferation and zinc concentration in pancreatic tissue yielded significant positive correlations, and the zinc concentration in pancreatic tissue was significantly correlated with both endo- and exocrine function and the pancreatic regeneration rate. These results suggest that a high-zinc diet after major pancreatectomy is effective in maintaining the zinc concentration in pancreatic tissue, which not only enhances early cell proliferation in the remnant pancreas but improves pancreatic endo- and exocrine function in the late period, promoting pancreatic regeneration.