Objective To prepare the polyclonal antibody against mouse HDAC2 and identify its reactivity and specificity. Methods An anti-peptide antibody has been developed by immunizing rabbits with a peptide synthesized according to the amino acid sequences of mouse HDAC2 protein. The peptide was coupled with KLH and injected into rabbits subcutaneously. The sera were collected and the antibody activity was evaluated with ELISA, Western blot and immunohistochemistry. Results The titer of the antibody in ELISA was estimated as high as 1:4000. Western blot assay of the brain extracts from the APP/PS1mice and HDAC2 peptide showed a positive band at 80kD when incubated with the antiserum. The immunohistochemistry stain show that the antiserum get the positive result with APP/PS1mice brain at the titer of 1:100, 1:200, 1:400, 1:800.Conclusion These antiserum have specific reactivity with HDAC2 in serum and tissue, and may possibly be applied in vivo and vitro in associated diseases.