The main objective of the present study was to test the hypothesis that exogenous insulin would enhance colon carcinogenesis. Thirty-six female Fischer 344 rats were fed ad libitum a low-fat rodent chow and given a single azoxymethane injection (20 mg/kg); one week later, they were randomized into two groups. Control rats were given a subcutaneous saline injection, 5 days/wk, and experimental rats were given Ultralente bovine insulin (20 U/kg). The promoting effect of insulin injections was assessed by the multiplicity (number of crypts) of aberrant crypt foci after 100 days of treatment (72 injections). The rats given insulin ate more and were heavier than controls (215 +/- 11 vs. 182 +/- 7 g, p < 0.001). Insulin injections also increased the amount of abdominal fat, plasma triglycerides, and insulinemia and decreased blood glucose (all p < 0.05). The number of aberrant crypt foci was the same in both groups, but their multiplicity was significantly increased by the insulin injections (2.8 +/- 0.3 vs. 2.5 +/- 0.2 crypt/focus in controls, p = 0.007). In addition, the proportion of sialomucin-producing foci was higher in insulin-injected rats than in controls (p = 0.04). These data show that exogenous insulin can promote colon carcinogenesis in rats and suggest that life-style and diets leading to low blood insulin might protect humans against colorectal cancer.