The small intestine is important for nutrient digestion and absorption as well as immune function. Newborns are sensitive to pathogen and diet-induced inflammation, which influences development of intestinal function. Butyrate has been shown to possess immune modulatory effect in various cells and tissues. But its effect on LPS-induced inflammation in the porcine IPEC-J2 intestinal cell model are unclear. Therefore, we investigated the effects of butyrate on expression of cytokines and metabolic gene markers in this cell line. A randomized complete block design was used. Main effect was the different concentrations of butyrate and replicate was used as the blocking factor. There were at least 6 replicates per treatment. Data were analyzed using PROC GLM. Gene expression was determined by RT-PCR. High concentration of butyrate (1mM) significantly increased (P < 0.05) LPS-induced TNFα, IL-6, IL-8 and MCP1 expression, and this indicated that this concentration was harmful to the cells. However, lower concentrations of butyrate (10 μM to 100 μM) significantly decreased (P < 0.05) LPS-induced MCP-1 and TLR4 expression (100 μM concentration) and IL-1β (50 μM) compared with control. Butyrate treatment also significantly increased expression of metabolic genes such as ACO (100 μM) and PPARα (10 to 100 μM), indicating that butyrate increases energy expenditure. LPS treatment significantly reduced ACO expression and eliminated the effect of butyrate on ACO and PPARα expression. Taken together, butyrate exhibited limited anti-inflammatory effect in IPEC-J2 cells, but strongly enhanced oxidative capacity through induction of oxidative genes.