Abstract Agents that increase natural protective mechanisms have been proposed for prevention and treatment of intramammary infections. The objectives of this study were to get an insight of innate immune mechanisms that occur during bovine mammary involution in both uninfected and chronically Staphylococcus aureus-infected glands and to describe the effects on those mechanisms of a single intramammary infusion of a LPS-based biological response modifier (BRM) at the end of lactation. Three groups of 12 cows, each one including 6 S. aureus-infected and 6 uninfected, were infused in two mammary quarters with BRM or placebo and sacrificed at 7, 14 and 21 d of involution. In uninfected and S. aureus-infected quarters treated with a BRM, the number of monocytes/macrophages detected with CD14 antibody was significantly higher ( P < 0.05) than in placebo-treated quarters at every sampling evaluation period. In uninfected quarters, the TNF-α staining area was not affected by BRM treatment. However, in infected quarters, the immunostained area for TNF-α was significantly higher than in uninfected quarters and BRM treatment was associated with increased staining at 21 d of involution.