To explore the effect of acute hypoxia on tau phosphorylation, rat brain slices were incubated at 37℃ for 30 min or 120 min with or without oxygen supply. Then tau phosphorylation was detected by Western blots. The results showed that significant dephosphorylation of tau at Ser-396/Ser-404, Ser-422 and Ser-199/Ser-202 was induced by acute hypoxia. The activity of protein phosphatase-2A (PP-2A) and the expression of PP-2A catalytic subunit were simultaneously increased. The results suggest that acute hypoxia induces dephosphorylation of tau and the up-regulation of PP-2A may be at least one of the underlying mechanisms.