Abstract: Objective To explore the correlation between Circadian Locomotor Output Cycles Kaput (CLOCK) gene polymorphisms and primary male infertility.Methods Totally 478 male infertility patients visiting Infertility Clinic of Affiliated Hospital of Nanjing Medical University from 2005 through 2010 were recruited as the cases and 194 attendees with normal reproductive history visiting other clinics of the same hospital during the same period were recruited as the controls.Five milliliters peripheral blood were collected from each participant with informed consent.An aliquot of each blood sample was used to separate the serum for the measurement of testosterone (T) and follicular stimulating hormone (FSH) using the standard radioimmunoassay.The rest of the blood sample was used to extract the DNA for the assay of three tagging single-nucleotide polymorphisms of CLOCK gene(rs1801260,rs3817444,and rs3749474) using real-time fluorescence quantitative PCR.Results The serum FSH concentration was significantly higher in the cases carrying TT and TC+CC genotype of rs3749474 locus than in the controls (P<0.05);the serum T concentration was significantly higher in the cases carrying CC genotype of rs3749474 locus than in the controls (P<0.05);the serum levels of FSH and T were significantly higher in the cases carrying AA genotype of rs1801260 locus than in the controls (both P<0.05);the serum FSH concentration was significantly higher in the cases carrying CC and CA+AA genotype of rs3817444 locus than in the controls (P<0.05).Conclusion The polymorphism of CLOCK gene is associated with the risk of primary male infertility and its mechanism needs further study.