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Huntington disease (HD) is an autosomal dominant inheritance neurodegenerative disorder. 3-Nitropropanoic acid (3-NP) is a mitochondrial toxin that induces HD-like symptoms and thus serves as a good experimental model of HD. Chrysin (5, 7-dihydroxyflavone) is a natural flavonoid that have multiple biological activities. The present work was aimed to evaluate the neuroprotective efficacy of Chrysin in rat brain, under the influence of 3-NP treatment, by studying neurobehavioral and biochemical alterations alongwith histo-architectural changes. Male Wistar rats (220–250 g) were used in the study and were divided into three groups following randomization. Each group comprised of nine animals. Group I animals served as control group and administered with normal saline (orally) as vehicle. Animals of Group II were treated with 3-NP for four successive days, at the dose of 20 mg/kg, intraperitoneally (i.p.). Animals that received Chrysin for the period of four consecutive days with the dose of 50 mg/kg, orally twice daily (30 min pre-treatment and 6 h post-treatment) following 3-NP administration served as Group III. After the treatment regime, animals were evaluated for neurobehavioral alterations and brain homogenates were used for estimation of neurotoxicity marker activity and neurotransmitter level along with histological assessment. The significant alteration in neurobehavioral, biochemical and neuronal structure in striatal part of brain was observed in the 3-NP administered (Group II) animals. It was observed that co-treatment of Chrysin with 3-NP treated rats the rotarod performance, grip strength, stride length as well as monoamine oxidase activity and serotonin levels were elevated. The results of this study reveal that Chrysin treatment alleviated the neurobehavioral, biochemical and histological alterations against HD symptoms in rats. [ABSTRACT FROM AUTHOR]