Background: This investigation was performed to examine the combined effects of protein malnutrition and chronic moderate amount of alcohol intake on insulin secretory capacity and sensitivity in growing rats. Methods: Weanling 4-week-old male Sprague-Dawley rats were fed low protein [5%, (wt/wt)] or control (C, 20%) diet from 4 to 12 weeks and alcohol (5g/kg/d) or saline gavage from 8 to 12 weeks. All rats were divided into the 4 groups according to different diet protocols: group 1 (protein-deficient alcohol rats), group II (protein-deficient saline rats), group III (protein-sufficient alcohol rats), and group IV (protein-sufficient saline or control rats), At the age of 12 weeks, we determined the insulin secretory capacity and sensitivity in the 4 different diet groups. Results: The results are summarized as following: 1. Normal weight gain was nearly completely arrested in protein-deficient rats compared to control rats. In protein-sufficient rats, chronic alcohol intake decreased body weight gain. Pancreatic weight adjusted with body weight was not different among the 4 groups, but epididymal fat weight adjusted with body weight was decreased in group II compared to group IV. 2. Intraperitoneal glucose tolerance was improved in group I compared to the other groups. Insulin responses to glucose challenge were markedly decreased in group II compared to group IV, but not in group l. 3. Glucose disposal rate during euglycemic clamp test was diminished in group II compared to qroup IV, but there were no differences between group I and group I 3. Glycogen synthase activities of skeletal muscle after 2 hour hyperinsulinemic state were not different among the 4 groups. 4. There were no differences of reserved insulin content of whole pancreas adjusted with pancreas weight among the 4 groups. 5. In light microscopic findings of pancreatic islets, sizes of islets, islet cells and nuclei were decreased in protein-deficlent rats compared to control rats. However, the sizes of islet cells and nuclei were further decreased in group II compared to group l. Conclusion: These results suggest that impaired insulin secretion and decreased insulin sensitivity due to protein malnutrition can be restored by chronic, moderate amount of alcohol intake, but these beneficial effects may not be appeared in protein-sufficient state. Therefore, the chronic alcohol intake differently influences glucose metabolism according to individual nutritional status, and further studies for the effects of alcohol intake in lean diabetic patients are required to extrapolate these resuits in human (J Kor Diabetes Asso 24:19-36, 2000).