Tau hyperphosphorylation and memory deficit are characteristic alterations of Alzheimer's disease (AD). Protein phosphatases (PP)2A plays a crucial role in AD-like lesions. Inhibition of PP2A through intracerebroventricular injection of okadaic acid (ICV-OKA) induces tau hyperphosphorylation and memory impairment. In the present study, we investigated the effect of naringin on ICV-OKA-induced cognitive impairment in rats. ICV OKA administration produced significant cognitive deficits as assessed by both Morris water maze and elevated plus maze task which is accompanied with significantly enhanced oxidative-nitrosative stress, acetylcholinesterase, and mitochondrial enzyme (I, II,III and IV) activities and surge in serum inflammatory cytokines (TNF-α, TGF-β and IL-1β. Chronic treatment with naringin, (50, 100 and 200 mg/kg; oral gavage) for 14 days significantly and dose dependently improved cognitive deficits in ICV-OKA rats along with mitigation of oxido-nitrosative stress mediated alterations in mitochondrial enzyme activities and serum inflammatory cytokines. Naringin produced comparable effects to rivastigmine (2mg/kg; po). Thus the study demonstrates the effectiveness of naringin in preventing cognitive deficits caused by ICV-OKA in rats and it may provide a novel and effective strategy to treat neurodegenerative diseases such as Alzheimer's disease.