Toll-like receptors (TLR) are a family of pattern recognition receptors identifying pathogen associated molecular patterns (PAMPs). They play a critical role in the innate immune response during the initial interaction between the infecting microorganism and phagocytic cells. Here, we verified the presence of TLR-2 in spleen, lymph node and thymus of Swiss albino mice and their modulation after infection with Staphylococcus aureus and Lipopolysaccharide (LPS) challenge. It was seen that TLR-2 gene transcribed to its respective mRNA on S. aureus infection, in thymus, spleen and lymph node of mice but their levels and mode of expression varied. When challenged with LPS no prominent changes in the expression of TLR-2 receptor was observed but its expression increased gradually with time in the thymus, spleen and lymph node of S. aureus infected mice. TLR-2 expression was also found enhanced in infected splenic macrophages. By studying the serum cytokine profile the functionality of the receptor was measured. The results indicate the presence of TLR-2 in thymus, spleen and lymph node of Swiss albino strain of mice and that they are modulated by S. aureus. © 2015 National Institute of Science Communication. All rights reserved.