BACKGROUND/AIMS: Sheep are important livestock with variant ovulation rate and fertility. Dorset sheep is a typical breed with low prolificacy, whereas Small Tail Han sheep with FecB mutation (HanBB) have hyperprolificacy. Our previous studies have revealed the gene expression difference between the ovaries from Dorset and HanBB sheep contributes to the difference of fecundity, however, what leads to these gene expression difference remains unclear. DNA methylation, an important epigenetic process, plays a crucial role in gene expression regulation. METHODS: In the present study, we constructed a methylated DNA immunoprecipitation combined with high throughput sequencing (MeDIP-seq) strategy to investigate the differentially methylated genes between the Dorset and HanBB ovaries. RESULTS: Our findings suggest the genes involved in immune response, branched-chain amino acid metabolism, cell growth and cell junction were differentially methylated in or around the gene body regions. CONCLUSIONS: These findings provide prospective insights on the epigenetic basis of sheep fecundity.