The cellular mechanisms of early weaning on intestinal development are not well established. To see if cell proliferation occurs in intestinal mucosa after early weaning, suckling rats were weaned precociously on postnatal day 15 and sacrificed 1, 2, 3, and 6 days after early weaning. Jejunal mucosa were assayed for ODC (ornithine decarboxylase), sucrase activities, protein and DNA contents. Jejunal cell proliferation was monitored by bromodeoxyuridine (BrdU) immunohistochemistry. The results demonstrated that increased jejunal ODC activity was the earliest cellular event to occur after early weaning. ODC increased at day 1 and peaked at day 3 (32-fold), followed by sucrase activity with increases at day 2 and peaked at day 3 (13-fold). The increase in BrdU immunostaining was seen at day 3. The increase of protein and DNA contents occurred at day 6. Serum corticosterone levels were increased on days 1 and 2 only. To explore if the intake of high carbohydrate rat chow was the causative factor, we also compared the induction of ODC activity in early weaned and fasted pups. Results showed that 1 day after early weaning ODC activity was not increased in the fasted group while the early weaned group showed 7-fold increase. These findings suggest early weaning stimulates jejunal cell proliferation as indicated by increased in both BrdU immunostaining and ODC activity. Increase in corticosteroid may be the trigger in the initial stage of the early weaning process but dietary factor also plays a role.