To investigate whether LEP G2548A and LEPR Gln223Arg gene polymorphism associated with the pathogenesis of unexplained infertility in north Indian population. This investigation randomly selected 229 female subjects of age group between 18 to 40 years (120 cases and 109 controls). At first, the members were classified into fertile and infertile. Further, they are separated based on BMI, non-obese (BMI: 18.5 to 24.5) and obese (BMI ≥ 25). The selected gene polymorphisms LEP G2548A and LEPR Gln223Arg were analyzed by polymerase chain response (PCR) followed by restriction fragment length polymorphism (RFLP). The univariate analysis reveals that Leptin, LEP G2548A and LEPR Gln223Arg genotypes, the most significant predictor of unexplained infertility (all p<0.05). The logistic regression analysis found that these three variables significant in multivariate analysis (all p<0.05) suggesting these as significant and independent predictors of unexplained infertility. The allele frequency of both LEP G2548A and LEPR Gln223Arg was found significantly different and higher in unexplained infertile than fertile. Moreover, the phenotype frequency of both LEP G2548A and LEPR Gln223Arg was also found significantly different and higher in unexplained infertile than fertile. G2548A was more frequent than LEPR Gln223Arg. This study suggested that high Leptin level and risk genotype increases the risk of infertility. Further investigations in other geographical region of India are to substantiate our finding.