This study examined the relationship of fasting serum glucose, insulin, C-peptide, glycosylated hemoglobin A (HbA1c), and Homeostasis Model Assessment (HOMA)-insulin resistance to risk of chronic kidney disease (CKD) among 6453 persons without diabetes (fasting glucose <126 mg/dl and not taking diabetes medication) who participated in the Third National Health and Nutrition Examination Survey and were aged 20 yr or older. CKD was defined as an estimated GFR <60 ml/min per 1.73 m(2). The prevalence of CKD was significantly and progressively higher with increasing levels of serum insulin, C-peptide, HbA1c, and HOMA-insulin resistance. After adjustment for potential confounding variables, the odds ratio of CKD for the highest compared with the lowest quartile was 4.03 (95% confidence interval [CI], 1.81 to 8.95; P = 0.001), 11.4 (95% CI, 4.07 to 32.1; P < 0.001), 2.67 (95% CI, 1.31 to 5.46; P = 0.002), and 2.65 (95% CI, 1.25 to 5.62; P = 0.008) for serum insulin, C-peptide, HbA1c levels, and HOMA-insulin resistance, respectively. For a one SD higher level of serum insulin (7.14 micro U/ml), C-peptide (0.45 Deltamol/ml), HbA1c (0.52%), and HOMA-insulin resistance (1.93), the odds ratio (95% CI) of CKD was 1.35 (1.16 to 1.57), 2.78 (2.25 to 3.42), 1.69 (1.28 to 2.23), and 1.30 (1.13 to 1.50), respectively. These findings combined with knowledge from previous studies suggest that the insulin resistance and concomitant hyperinsulinemia are presented in CKD patients without clinical diabetes. Further studies into the causality between insulin resistance and CKD are warranted.