Insulin resistance, which is highly prevalent in the elderly, is suggested to be accompanied by an increased acute phase response. Until now, it is unclear whether cellular adhesion molecules are involved in the clustering of insulin resistance. In the present study, we examined the relationship of insulin resistance (measured by postload insulin) with levels of markers of inflammation and cellular adhesion molecules in a random sample of 574 nondiabetic elderly men and women participating in the Rotterdam Study. Associations were assessed by regression analysis, with ln-insulin as the dependent variable [regression coefficient (95% confidence interval)]. In our population, insulin was strongly and significantly (P < 0.001) associated with the markers of inflammation C-reactive protein [1.52 (0.96-2.08)], alpha-1-antichymotrypsin [1.25 (0.82-1.69)], and IL-6 [2.60 (1.69-3.52)], adjusted for age and gender. Associations weakened, to some extent, after additional adjustment for measures of obesity, smoking, and cardiovascular disease. Insulin was associated with the soluble intercellular adhesion molecule 1 [2.22 (1.29-3.16; P < 0.001)], whereas no association with the soluble vascular cell adhesion molecule 1 was found. The strength of the associations of insulin with C-reactive protein, alpha-1-antichymotrypsin, IL-6, and soluble intercellular adhesion molecule 1, as assessed by standardized regression coefficients, was comparable with the strength of the associations of insulin with high-density lipoprotein cholesterol, body mass index, and waist-to-hip ratio. The results of this population-based study indicate that low-grade inflammation and the cellular adhesion molecule soluble intercellular adhesion molecule 1 are an integral part of insulin resistance in nondiabetic elderly. These factors may contribute to the well-known relationship between insulin resistance and cardiovascular disease risk and might potentially become therapeutic targets in insulin resistant subjects.