This study investigated the time-course of the nociceptive neuropeptide substance P and nerve growth factor (NGF), which facilitates substance P production, in lumbar and cervical dorsal root ganglia (DRG) of streptozotocin-induced diabetic rats. Levels of substance P and NGF were measured by radioimmunoassay and sandwich enzyme-linked immunosorbent assay, respectively, 2 months, 4 months and 8 months after induction of diabetes, and compared with age-matched non-diabetic control rats. At 2 months and 4 months, substance P and NGF levels were lower in the lumbar DRG of the diabetic rats than in controls. At 8 months, substance P and NGF were lower in both the lumbar and cervical DRG of the diabetic rats than in controls. These data demonstrate that a decrease in substance P levels in primary sensory neurons with NGF depletion occurs in an axonal length-dependent manner in diabetic rats, and that this decrease may be correlated with the duration of diabetes.