We investigated the effect of Prostaglandin E1 in lipid microspheres (Lipo-PGE1) on diabetic peripheral neuropathy from view of symptoms, neurological examinations including sensory threshold evaluated with Semmes-Weinstein monofilaments (SWM). Type 2 diabetic patients with diabetic peripheral neuropathy were participated in this study. The patients were randomly assigned to two groups, 11 Lipo-PGE1-treated patients and 16 control patients. Lipo-PGE1 at a dose of 10mg in 20ml of saline was injected intravenously as a bolus once daily for 2 weeks. Before and, 1, 2 and 4 weeks after the start of treatment with Lipo-PGE1, sensory threshold was evaluated with Semmes-Weinstein monofilaments at total 18 touch sites on the feet. Administration of Lipo-PGE1 improved subjective symptoms especially in items of numbness and imperception. Such improvement in subjective symptoms correlated well with the improvement in Semmes-Weinstein monofilaments examination, whereas the improvement was not recognized in motor nerve conduction velocity (MCV), sensory nerve conduction velocity (SCV) and coefficient variation of R-R interval on ECG (CVR-R). The improvement lasted for at least 6 months. This study demonstrated that Lipo-PGE1 has long term amelioration effects on diabetic neuropathy especially in symptoms and sensory threshold, and that Semmes-Weinstein monofilaments examination is a simpler, more valid and quantitative tool for assessing the clinical effect of Lipo-PGE1 on diabetic peripheral neuropathy.