|G-CSF(Granulocyte-colony stimulating factor) has been suggested to have neuroprotective effect on the central nervous system. However, it is difficult to expect this beneficial effect on all neuronal tissues. Therefore, we investigated that G-CSF is also beneficial in the protection of peripheral nerve damage of experimental diabetes(DM). Male Sprague-Dawley rats were divided into 5 groups as follows: Normal, Normal+G-CSF(50 ug/kg for 5 days), DM, DM+G-CSF (G-CSF, 50 ug/kg for 5 days), and DM+ G-CSF extension(G-CSF, 50 ug/kg for 5 days and followed by two injections per week up to 24 weeks). In the result, body weight and blood glucose levels were not affected by G-CSF administration and current perception thresholds (CPT) were also not different significantly according to G-CSF treatment. The number of gastric small nerve fibers penetrating into mucosa (a) and intraepidermal nerve fibers (IENF) density of the foot (b) were also not different significantly among DM groups irrespective of G-CSF administration although mild reduced trend in the nerve damage was observed in the G-CSF treated groups as follows (DM vs. DM+G-CSF vs. DM+G-CSF extension, respectively). (a) Gastric small nerve fiber; 0.85±0.28 vs. 1.21±1.01 vs. 1.42±1.02, p>0.05 (b) IENF density; 4.90±0.32 vs. 5.21±0.24 vs. 5.69±0.33, p>0.05. Our results indicate that diabetic peripheral neuropathy (DPN) caused by diverse pathogenic mechanisms is difficult to be protected completely by sole G-CSF treatment and neuroprotective effect of G-CSF may be dependent on the neuronal type or distribution. G-CSF receptor presence or not is also considered to be important factor in this regard. However G-CSF combination with well known strategies including strict glucose control and oxidative stress lowering agents is worth investigating for novel DPN therapeutic approach.