Bovine peptidoglycan recognition protein 1 (PGLY RP1) is an important receptor that binds to murein peptidoglycans (PGN) of Grampositive and Gram-negative bacteria and is, therefore, involved in innate immunity. The SNP T>C rs68268284 located in the 1st exon of the PGLYRP1 gene was identified by the PCR-RFLP method in a population of 319 Holstein cows. Somatic cell count (SC) was measured 7–10 times in each of three completed lactations to investigate whether the PGLYRP1 polymorphism is associated with SC. Using the GLM model, it was found that cows with the TT genotype showed significantly lower somatic cell counts than those with the CC genotype during the first lactation (P = 0.023). Moreover, during lactations 1–2 and 1–3, cows with the TT genotype reveal significantly lower SCC than CT heterozygotes, at P = 0.025 and P = 0.006, respectively. Computer-aided analysis showed that rs68268284 polymorphism could modify the PGLY RP1 functions because the mutated residue is located in a domain that is important for the binding of other molecules.