Proteomics, a hot new research area studied by biologists in the post-genome era, leads an integrated study of the expression and function of proteins on a large scale. Epididymis is responsible for the sperm maturation and storage, and its gene expression is highly region-specific, so it maybe an ideal model for proteomics, especially for differential proteomics study. This paper gives a brief introduction of the application of proteomics in the epididymis and the differential proteins expressed in different epididymal regions. These epididymis-specific/selective proteins identified by proteomics technology may prove to be targets for contraception or may provide insight to the unique responsibilities of the epididymis in supporting male fertility.