Because high waist-to-hip ratio (WHR) and high serum insulin levels have been reported to be associated with an increased risk of prostate cancer, we assessed the relationship between insulin resistance and prostate cancer risk in Chinese men. We measured fasting serum glucose and insulin levels in 128 case and 306 control subjects and used the homeostasis model assessment to derive indices of insulin sensitivity and resistance. Relative to men in the lowest tertiles, men in the highest tertile of insulin sensitivity had a reduced risk of prostate cancer (odds ratio [OR] = 0.35, 95% confidence interval [CI] = 0.21 to 0.60), but men in the highest tertile of insulin resistance had an increased risk of prostate cancer (OR = 2.78, 95% CI = 1.63 to 4.72). Considering insulin resistance and WHR together, the effect of insulin resistance was apparent in all tertiles of WHR, with men in the highest tertile of insulin resistance and WHR having the highest risk (OR = 8.21, 95% CI = 2.84 to 23.70). The associations between prostate cancer risk and insulin sensitivity or resistance were independent of total caloric intake and serum levels of insulin-like growth factors, sex hormones, and sex hormone-binding globulin. Because of the retrospective design of this study, the role of insulin resistance in prostate cancer needs to be confirmed in prospective studies.