This study was designed to investigate neuro-behavioral, neuro-biochemical and neuro-morphological alterations induced by sub-acute toxicity of lead (Pb) in male Wistar rats as well as the assessment of the neuroprotective effect of thiamine hydrochloride against Pb-induced behavioral, biochemical and morphological neuro-alterations. For this purpose 24 male Wistar rats were randomly divided into 4 groups (n=6). Rats in the 1^st group were treated with lead acetate orally at dose of 100 mg/kg b.wt. Animals in 2^nd group were received leaded water orally + 100 mg/kg thiamine hydrochloride intraperitoneally. 3^rd group were treated only with thiamine hydrochloride. 4^th group was served as the control animals. Animals were exposed to treatments once daily for 7 consecutive days. Behavioral alterations were assessed by applying neurological tests as elevated plus-maze and Morris water maze. The main neurotransmission systems as cholinergic, adrenergic, serotonergic and GAB Aergic were evaluated in brain tissue homogenate. Morphological alterations was assessed histopathologically. Results revealed that, Pb exposure caused spatial learning and memory impairment, as well as a significant increase in the content of acetylcholine, serotonin and norepinephrine while the activity of acetylcholinesterase and GABA content showed a significant decrease. Hemorrhage in brain, mild perivascular edema and perivascular cuffing were the main pb-induced morphological alterations. Simultaneous administration of thiamine markedly ameliorated Pb-induced neurotoxicity which was indicated by comparatively better behavioral performance, alleviation of the neurotransmitters disturbances and decreased the severity of histopathological lesions. In conclusion, thiamine has been found to be extremely significant in the fighting of Pb-induced neuro-manifestations.