The investigators initial study opened the way for randomized trials that monitor the effects of acetylcholine (Ach) iontophoresis vasodilators on endothelial nitric oxide synthetase (NOS) to develop a transdermal treatment that is effective, free from systemic adverse effects.

The investigators studied endothelial-mediated microvascular blood flow in neuropathic diabetic patients to determine the association between endothelial regulation of the microcirculation and the expression of endothelial constitutive nitric oxide synthetase (NOS). As a result, the nerve fibers can become damaged. Once the nerves have been damaged they cannot repair themselves.

Material and methods:

A group of 80 patients (male and female) diagnosed as type 2 diabetes mellitus, will be included in the study their age ranged from 40-60 years. Patients randomly will be divided into two groups:

Study groups (A) 40 patients type 2 diabetes mellitus with clinically proved peripheral neuropathy. And control group (B) 40 patients with asymptomatic type 2 diabetes mellitus. They were selected from south valley university hospitals. Group (A) receive iontophoresis by acetylcholine with (15) min for three sessions per week for four weeks. Also the investigators followed up study group (A) one month of aerobic exercises in form of 15 minute walking, bicycling, or swimming, and the investigators reevaluated nitric oxide level. Group (B) received shame iontophoresis with (15) min for three sessions per week for four weeks.

Inclusion Criteria:

• Patients have to be symptomatically stable with type 2 diabetes mellitus complicated with peripheral neuropathy.
• Optimized pharmacological treatment that will be remained unchanged throughout the study.

Exclusion Criteria:

• Implanted cardiac pacemakers.
• Patients with known skin allergies.
• Presence of skin inflammations.
• Peripheral vascular disease.