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In the present study we evaluated the effect of methanol root extract of Plumbago zeylanica L. on central nervous system. The methanol root extract of Plumbago zeylanica was investigated in a battery of behavior models (hole board, locomotor, and forced swim) in mice. Roots of Plumbago zeylanica L. have several therapeutic applications in folk medicine some authors also reported thepoisonous and toxic properties of the plant roots. In the present study methanol root extractproduced significant effect on the nervous system at the doses of 160 mg/kg ( i.p route) compared toreference drug diazepam (DZP) and fluoxetine. The brain catalase activities was significantly decreased(p<0.05) and Lactate dehydrogenase enzyme increased significantltly (p<0.05) when compared thetreated group with control. The catalase and LDH activities of cerebral cortex region showed highlysignificant (**p< 0.01) when compared with mid brain region in treated group. In conclusion, resultssuggest that the methanol root extract of Plumbago zeylanica L. possess potent effect on nervous system and disturbances in enzyme activities in mice brain.