Patients with diabetes are at increased risk for adverse events after coronary stenting, perhaps reflecting a pro-inflammatory state. To characterize the inflammatory response to coronary stenting in patients with and without diabetes, blood samples were obtained from 75 patients before stenting and 10 minutes, 1 hour, and 24 hours later. C-reactive protein (CRP, microg/ml), interleukin (IL)-6 (pg/ml), IL-1 receptor antagonist (pg/ml), and soluble CD40 ligand (ng/ml) were assayed in each sample by enzyme-linked immunosorbent assay. Concentration changes after stenting were identified by repeated-measures analysis of variance. Multivariate analysis was performed to delineate independent predictors of increased concentrations of inflammation markers. Overall, 88% of patients had acute coronary syndromes; 36% had elevated markers of cardiac injury. The preprocedural concentrations of CRP in those with diabetes were more than twice as high as those in patients without diabetes. Two independent predictors of elevated preprocedural CRP concentrations were diabetes (odds ratio 3.95, 95% confidence interval 1.17 to 13.4) and a cardiac marker-positive acute coronary syndrome (odds ratio 3.70, 95% confidence interval 1.22 to 11.2). Preprocedural concentrations of IL-6, IL-1 receptor antagonist, and soluble CD40 ligand tended to be greater in patients with diabetes. The increase in CRP after stenting was much greater for patients without diabetes compared with that in patients with diabetes such that the apparent intensity of inflammation after 24 hours was similar in those with and without diabetes. Thus, patients with and without diabetes exhibit different inflammatory responses to stenting, reflecting the lower preprocedural inflammation in those without diabetes versus those with diabetes.