Cognitive impairment is a common feature of both lead exposure and hyperphosphorylation of tau. We, therefore, investigated whether lead exposure would induce tau hyperphosphorylation. Wistar rat pups were exposed to 0.2% lead acetate via their dams' drinking water from postnatal day 1 to 21. Lead in blood and brain were measured by atomic absorption spectrophotometry and the expression of tau, phosphorylated tau and various serine/threonine protein phosphatases (PP1, PP2A, PP2B and PP5) in the brain was analyzed by Western blot. Lead exposure significantly impaired learning and resulted in a significant reduction in the expression of tau but increased the phosphorylation of tau at Ser199/202, Thr212/Ser214 and Thr231. PP2A expression decreased, whereas, PP1 and PP5 expression increased in lead-exposed rats. These results demonstrate that early postnatal exposure to lead decrease PP2A expression and induce tau hyperphosphorylation at several serine and threonine residues. Hyperphosphorylation of tau may be a mechanism of Pb-induced deficits in learning and memory.