This study is to clarify whether C-reactive protein (CRP) and white blood cell (WBC) count influence insulin homeostasis to the same degree. Serum CRP and peripheral WBC were measured in 739 subjects with normal glucose regulation, 512 with impaired glucose regulation, and 502 newly diagnosed diabetic patients. Levels of insulin resistance (IR) were assessed using the index of homeostasis model (HOMA-IR). Serum CRP and WBC were significantly correlated with HOMA-IR and risk factors of IR. Relative risks of IR for each 1-SD increase of Ln (CRP) and Ln (WBC) were 1.28 (1.10-1.47) and 1.15 (1.01-1.31), respectively after adjustment for age, sex, obesity measurements, and other traditional risk factors. Additional adjustment for WBC slightly attenuated the association between CRP and IR [1.25 (1.08-1.45); P = 0.003] whereas adjustment for CRP substantially attenuated the association of WBC with IR toward null (P = 0.134). Moreover, individuals with both high levels of CRP and WBC were at higher risks of IR than those with high CRP or WBC alone. Both CRP and WBC were significantly associated with risks of IR. CRP might be a more effective biomarker in terms of the association with IR.