Background and Aim: Toll-like receptors (TLRs) are important for the recognition of pathogen-associated molecular patterns. Single nucleotide polymorphisms (SNPs) within TLRs have a potential impact on the alteration of susceptibility or resistance to inflammatory diseases. This work focused on a case-control study for the distribution of SNPs in TLR2 gene to test their role for endometritis occurrence in river buffalo.
 Materials and Methods: Egyptian buffaloes from the slaughterhouse were tested, where forty samples divided into apparently healthy uteri (20n) and clinically infected ones (20n) were used to detect the genetic association between TLR2 gene SNPs and endometritis disease.
 Results: Nineteen novel polymorphic sites were identified. Three SNPs were found to be statistically significant. AA genotype at 5`UTR and CC genotype at the coding region had significant association with susceptibility to endometritis, while GG genotype at 5`UTR had significant association with resistance to endometritis. Polyphen 2 analysis revealed three amino acids substitutions in TLR2 protein having potential functional significance. Haplotype reconstruction revealed the statistical significance of haplotype frequencies between cases and controls indicating its association with the occurrence of endometritis.
 Conclusions: It is to be concluded that the innate immune activation response may be interfered by the effect of polymorphisms and mutations of TLRs due to the reduction of the protein ability to recognize Pathogen associated Molecular pattern (PAMPs).