Objective To investigate the mechanism of tanshinone in treatment of rats with Alzheimer's disease (AD).Methods 10 μg incubated Aβ 1-40 was injected bilaterally into the hippocampus of each rat.The level of acetylcholinesterase (AChE) in hippocampus of rats was examined with the method of AChE histochemistry.Immunohistochemistry and Western blot were used to determine the expression of neuronal nitric oxide synthase(nNOS)/inducible form of NOS (iNOS) in hippocampus of rats.Results The level of AChE positive fibers in hippocampus after hippocampal injection of Aβ 1-40 decreased as compared with controls.Both immunohistochemistry and Western blot showed that the expression of nNOS in models was downregulated whereas the iNOS was upregulated.With tanshinone administration,the changes mentioned above were improved.Furthermore,the percentage area with AChE positive fibers in each subfield of hippocampus was negatively correlated with the number of iNOS positive cells.Conclusion Tanshinone could remarkably modulate the levels of AChE and NOS proteins in hippocampus of rats with AD.This may be one of the therapeutic mechanisms of tanshinone in rats with AD.