Substance P is one of the neurotransmitters released by primary nociceptive neurons in the dorsal horn of the spinal cord and it binds postsynaptically to NK1-receptors. This receptor is therefore an obvious target for analgesic drugs. The aim of this multicenter, randomised, double-blind, placebo-controlled and parallel-group study was to test if the non-peptide NK1-receptor antagonist TKA731 would relieve painful diabetic polyneuropathy. Eighty-seven patients completed a treatment period of 2 weeks' duration with TKA731 (150 mg daily) or placebo preceded by one week for baseline observations. There was no significant difference between TKA731 and placebo in change in pain rating from baseline to study end neither for rating of total pain (mean −13.4 mm vs. −11.6 mm, p = 0.664) nor for change in ratings of different pain symptoms (touch- or pressure-evoked pain, pain paroxysms, steady burning or deep aching pain) (p = 0.169-0.834).