Subacute ruminal acidosis (SARA) has emerged as a prevalent digestive disorder that significantly affects the overall health of ruminants, with notable links to various inflammatory diseases. Throughout the progression of SARA, elevated lipopolysaccharide (LPS) levels in the rumen play a crucial role in initiating the innate immune response. In this review, we evaluate the recent insights into the pathways associated with SARA-induced inflammatory responses, with a specific focus on LPS. It is important to recognize the variation in the immune response activation potential of LPS derived from different bacterial sources. This variability aligns with the widespread detection of LPS in the rumens of ruminants with SARA. Nonetheless, trained immunity is expected to become a novel strategy for the prevention and control of SARA. This mechanism offers a rapid response to secondary stimuli, including LPS, effectively preventing inflammation. Ultimately, this review establishes a comprehensive system integrating SARA, LPS, and trained immunity. Through this integrated approach, we aim to provide innovative solutions to the challenges associated with SARA.