The present study aimed at detecting the association of ovine major histocompatibility complex class II (Ovar II) DRB1 gene second exon and susceptibility or resistance to hydatidosis in three sheep breeds of Sinkiang. The MHC-DRB1 second exon was amplified by polymerase chain reaction (PCR) from DNA samples of healthy sheep and sheep with hydatidosis. PCR products were characterized by the restriction fragment length polymorphism (RFLP) technique. Five restriction enzymes, MvaI, HaeIII, SacI, SacII, Hin1I, were used, yielding 14 alleles and 31 restriction patterns. Frequencies of patterns MvaIbc, Hin1Iab, SacIIab, HaeIIIde, HaeIIIdf, HaeIIIdd (P < 0.01) in Kazakh sheep, SacIab (P < 0.05) in Duolang sheep, and HaeIIIab, HaeIIIce, HaeIIIde, HaeIIIee (P < 0.01) in Chinese Merino (Sinkiang Junken type) sheep, were significantly higher in healthy sheep compared with infected sheep. These results indicated a strong association between these patterns and hydatidosis resistance. In contrast, the frequencies of MvaIbb, SacIIaa, Hin1Ibb, HaeIIIef (P < 0.01) and HaeIIIab (P < 0.05) in Kazakh sheep, SacIbb, HaeIIIae, Hin1Iab (P < 0.05), HaeIIIaa, HaeIIIbe, HaeIIIef (P < 0.01) in Duolang sheep, SacIIaa (P < 0.05) and HaeIIIbd, Hin1Ibb, HaeIIIcf, HaeIIIef (P < 0.01) in Chinese Merino sheep (Sinkiang Junken type) were significantly lower in healthy sheep compared with infected sheep. This indicated a strong association between these patterns and hydatidosis susceptibility. In addition, sheep with the pattern of HaeIIIef demonstrated a high hydatidosis susceptibility (P < 0.01) in all three breeds, while sheep with the pattern HaeIIIde demonstrated significant hydatidosis resistance (P < 0.01) in Kazakh and Chinese Merino sheep (Sinkiang Junken type). These results suggest that the Ovar-DRB1 gene plays a role in resistance to hydatidosis infection in the three sheep breeds.