Aim <p>To investigate the possible neuroprotective effect of low-intensity ultrasound (US) application against diabetic neuropathy.</p> Methods <p>Adult male wistar rats were randomly divided into three groups as control, untreated diabetic and US-treated diabetic. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50&#xa0;mg/kg) to the rats and verified by the presence of hyperglycemia (&gt; 250&#xa0;mg/dl). US was applied to sciatic nerve at a power density of 1.5&#xa0;W/cm² and a frequency of 1&#xa0;MHz for 3&#xa0;min/day for 5 weeks over a 5 cm² skin surface. Blood glucose, insulin and HbA1c levels were measured. Nociceptive hot plate test and electrophysiological measurements were performed. Oxidative stress and inflammation markers were also examined.</p> Results <p>Diabetes led to increases in blood glucose, HgA1C, nociceptive response times, oxidative stress and neuroinflammation, but decreases in insulin and nerve conduction velocity. With the applied US treatment, these values indicative of diabetic neuropathy consistently approached those of healthy controls.</p> Conclusion <p>Low-intensity ultrasound treatment of sciatic nerve appears to be neuroprotective in diabetic neuropathy as it effectively alleviates the neurophysiological and inflammatory changes associated with the glucose irregularity.</p>