Abstract—The objective of present study was to evaluate the in vivo effect of Bacopa monnieri leaf extract (100 mg/kg) and acephate (37.8 mg/kg) on Acetylcholinesterase (AChE) activity, kinetics and histology of cerebral cortex and hippocampus of brain of male albino rat. AChE activity was measured spectrophotometrically according to the method of Ellman et al..The acephate inhibited AChE activity strongly in cerebral cortex (72.5%; P < 0.02) than in hippocampus (55.6 %; P < 0.02). Bacopa monnieri similarly elicited higher AChE inhibition in cerebral cortex (51.6 %; P < 0.05) than in hippocampus (38 %; P < 0.01). However, synergistic inhibitory effect was recorded in rats pretreated with Bacopa monnieri followed by acephate exposure. Kinetic study of treated groups demonstrated competitive AChE inhibition in the brain regions, which was evident by increased Km and unchanged Vmax values against the control group. The histopathological examinations showed degeneration of pyramidal cells, deformity of neurocytes and vacuole formation in cytoplasm. These changes were pronounced with acephate. Our result shows that Bacopa monnieri has anti-cholinesterase potential hence it could provide novel pharmacological leads of potential benefit to the treatment of Alzheimer’s disease and therefore warrant further investigation.