Background: Oxidative stress is one of the molecular mechanisms in chlorpyrifos toxicity. The present study was designed to evaluate the attenuating effect of vitamin C on chlorpyrifos-induced alteration of neurobehavioral performance and the role of muscle acetylchloinesterase (AChE), glycogen and lipoperoxidation in the accomplishment of this task. Materials and Methods: Male rats were randomly assigned into 4 groups with the following regimens: soya oil (S/oil), vitamin C (VC), chlorpyrifos (CPF) and vitamin C+CPF (VC+CPF). The regimens were administered by gavage once daily for a period of 17 weeks. Neurobehavioral parameters measuring efficiency of locomotion, motor strength, righting reflex and excitability were evaluated at day 0 (pretreatment value), weeks 8 and 16. The rats were sacrificed at week 17 and evaluated for muscle glycogen and malonaldehyde (MDA) concentrations and AChE activity. Results: The result showed that deficits in locomotion efficiency, motor strength, righting reflex and excitability score induced by chronic CPF were mitigated but not completely abolished by vitamin C. The reduced muscle AChE activity and concentrations of glycogen and MDA evoked by chronic CPF were ameliorated by vitamin C. Conclusion: The study therefore showed that improvement in muscle AChE activity, glycogen concentration and reduced lipoperoxidation by vitamin C may be partly responsible for the mitigation of the chronic CPF-induced sensorimotor performance.