Injury to microvessels caused by the chronic consumption of sucrose can be prevented by selenium (Se). The objective of this study was to determine the temporal sequence of changes in serum triglycerides, total cholesterol, glucose, and insulin induced by sucrose and their relationship to Se status and microvascular injury. Two groups of 24 Wistar rats were fed ad libitum diets in which the entire carbohydrate was either corn starch or sucrose. Two other groups were fed identical diets supplemented with 0.1 micrograms Se/g. At 6, 8, and 10 mo, eight rats from each group were fasted for 12 h and had blood taken. Rats were then given a glucose tolerance test and killed, and their retinal microvessels were evaluated for injury. After 6 mo, sucrose-fed rats had elevated triglycerides and total cholesterol. Abnormal glucose clearance and hyperinsulemia developed after 8 mo. Evidence of microvascular injury became apparent after 10 mo. These changes did not occur in rats provided the starch-based diets, and microvascular injury did not develop in the sucrose-fed rats provided supplemental Se. Glutathione peroxidase activity was normal in all groups throughout the 10-mo experiment. These results chronicle the sucrose-induced systemic insult and show that the protective effect of Se does not occur by diminishing this insult to the microvessels.