In this study, we intended to investigate the impact of fibrates treatment on M. smegmatis infected cells, and observed that pretreatment of differentiated U937 cells with fibrate affects the expression of PPAR-α, which is a target receptor of fibrates, myeloid differentiation primary response gene 88 (MyD88), which participates in the immune response, and acetyl coenzyme A acetyl transferase-1 (ACAT-1), which participates in TNF-α activation and early cholesterol pathway, consequently alleviated infection by M. smegmatis in macrophages. Here, TNF is linked to infection.