Manganese (Mn) is an essential metallo enzyme component that in high doses can exert serious oxidative and neurotoxic effects. The aim of this study was to investigate the potential effect of acetylcholinesterase (AChE) activity, ACh content and Histochemical Studies in both low dose (2.5 mg/kg bw) and high dose (5 mg/kg bw) of Manganese (Mn) treated young and adult (2 months and 4 months) rat brain with reversal effect of alpha- tocopherol. In this study, it was observed that the AChE activity and ACh content in synaptosomal fraction of low dose and high dose of Mn-exposed rats showed decrease in AChE activity and increase in ACh content at both the ages (2 months and 4 months) when compared to control. However, the AChE activity was increased and ACh content was decreased in the animals supplemented with α-tocopherol along with Mn- exposure. In this study, we have also examined the histochemical studies in adult rat brain i.e, Cerebral Cortex, Hippocampus and Cerebellum. Histochemical staining of AChE in cerebral cortex, hippocampus and cerebellum of control adult rats showed increase of AChE staining and the animals treated with Mn showed loss of AChE staining in three brain regions. However, the administration of Alpha-tocopherol along with Mn showed increase of AChE staining. Among the three brain regions studied, Hippocampus showed maximum activity followed by Cerebral Cortex, and then Cerebellum. The above findings suggest that short-term Mn in vivo administration causes a statistically significant decrease in AChE activity. The Mn toxicity was reversed with Alpha-tocopherol co-administration which could thus be considered for future applications as a neuroprotective agent against chronic exposure to Mn and the treatment of manganism.