While brain kinin B1 receptor (B1R) is virtually absent in control rats, it is induced by the oxidative stress in various peripheral tissues and the spinal cord in type 1 and type 2 diabetic models. In the model of insulin resistance induced by high glucose feeding, B1R is associated with pain neuropathy, insulin resistance and hypertension. This study aims at determining whether B1R is also induced in the brain of glucose-fed rats via the oxidative stress and whether it can affect nocifensive behaviour. Male Sprague-Dawley rats (50-75 g) received either 10% D-glucose in their drinking water or only tap water (controls) and were maintained under a normal chow diet or a diet enriched with alpha-lipoic acid (antioxidant, 1g/kg diet) for 12 weeks. An intracerebroventricular (i.c.v.) guide cannula was implanted into the right lateral brain ventricle in isoflurane anesthetised rat 7 days before initiating experiments. After completion of experiments, rats were anaesthetized with CO2 inhalation and killed to collect the brain, which was frozen in 2-methyl butane cooled at -45°C with liquid nitrogen and kept at -80°C for determining B1R binding sites by autoradiography with [125I]-HPP-des-Arg10-Hoe 140 (150 pM) on brain tissue sections. Behavioural activity to the selective B1R agonist, Sar-[D-Phe8]-des-Arg9-BK (10 µg/1µl, i.c.v.) was measured before and after treatment with receptor antagonists (10 µg/1µl, i.c.v.) for B1 (SSR240612, R-715), substance P NK-1 (RP-67580) and glutamate NMDA (DL-AP5). Other studies included the nitric oxide synthase (NOS) inhibitor L-NNA (10 µg/1µl, i.c.v.). Results showed striking increases in the density of specific B1R binding sites in various areas of the cortex, diencephalon, basal ganglia, mesencephalon and medulla of glucose-fed rats in comparison with age-matched control rats. The latter increases in B1R binding sites were prevented by the antioxidant diet in all studied brain areas. The B1R agonist had no effect in control rats, yet it induced significant behavioural manifestations in glucose-fed rats (face washing, sniffing, head scratching, rearing, teeth chattering, grooming, digging, licking, biting, wet-dog shakes) when compared to aCSF. These responses were prevented by all antagonists and the inhibitor tested. The same pharmacological treatments had no direct effect on behaviour in the absence of B1R agonist. Data suggest that kinin B1R is induced and up-regulated by the oxidative stress in the brain of glucose-fed rats and that its intracerebral activation induces stereotypic nocifensive behaviour involving the release of several central mediators, notably substance P, glutamate and nitric oxide.