Evaluating insulin secretion ability and sensitivity is essential to establish an appropriate treatment for patients with type 2 diabetes. The serum C-peptide response (CPR) level is used to evaluate the quantity of endogenous insulin secretion. However, the serum CPR level alone cannot indicate insulin-secretion ability or insulin sensitivity, because plasma glucose levels influence endogenous insulin secretion and vice versa. The CPR index, a ratio of serum CPR level to plasma glucose concentration when measured simultaneously, was previously reported to be a useful marker to determine the necessity of insulin treatment in patients with type 2 diabetes, but the reasons are unknown. The aim of this study was to clarify which factors affect the CPR index in patients with type 2 diabetes. Totally, 121 subjects were included in this study; all participants were hospitalized for type 2 diabetes. On the day after admission, we calculated the CPR index from each patient's fasting blood sample and a blood sample taken 2 hours after breakfast (the postprandial sample). A detailed medical history was taken from each patient to establish the disease duration. The degree of diabetic retinopathy judged by an ophthalmologist was obtained from patients' medical records. An oral glucose tolerance test and a glucagon load test were performed after the fasting plasma glucose level decreased to 130 mg/dl, and indices of insulin secretion and sensitivity were calculated. Fasting and postprandial CPR indices were moderately correlated with total endogenous insulin secretion after oral glucose load and with the CPR level after glucagon load, insulin sensitivity, composite index, and the reciprocal index of homeostasis model assessment (HOMA-R-1). Furthermore, there was a weak but significant correlation between the postprandial CPR index and the duration of diabetes. The postprandial CPR index was inversely correlated with the degree of diabetic retinopathy, which is known to be associated with the duration of hyperglycemia. Our data clearly shows that the CPR index is a useful parameter to reflect the degree of impaired glucose tolerance.