Abstract: Background and Objective: Recent studies have revealed that monoamine oxidase-B (MAO-B) inhibitors effective in treating Alzheimer’s disease (AD), with a promotable extension of life span. It modulates nitric oxide (NO), which contribute to cognitive function in AD. The present study investigated the potential of protocatechuic acid (PCA) as MAO-B inhibitor and its effect on release of MAO, TNF-α, acetylcholine esterase enzyme, in cognitive dysfunctions associated with experimental dementia in rats. Materials and Methods: Aluminium chloride (AlCl3) was administered at a dose of 175 mg kg–1 per oral (p.o) for a period of 25 days in rats and then divided into different groups, i.e. standard group, negative control and two groups of PCA, (at a dose of 10 and 20 mg kg–1, p.o.), where these groups treated and observed until the 35th day of experimental trial. Morris water mazes (MWM), photoactometer test were performed on 5th, 16th, 26th and 36th day to access learning, memory and ambulatory movements. Later, the animals were sacrificed for biochemical and histopathological studies. Extent of oxidative stress was measured by estimating the levels of Glutathion (GSH), superoxide dismutase (SOD), nitrite, catalase. Brain acetylcholine esterase activity and MAO-A, MAO-B were also estimated. The brain levels of TNF-α was measured as marker of inflammation. Results: AlCl3 produced a marked decline in MWM performance and ambulatory movements’ of animals, reflecting impairment of memory and learning. PCA treatment significantly modulates AlCl3 induced memory deficits, biochemical and pathological alterations. Conclusion: The findings demonstrated that the memory restorative ability of PCA may be attributed due to its anti-cholinesterase, anti-oxidative and anti-inflammatory potential.