Proanthocyanidins are oligomers and polymers of flavan‐3‐ols that are amongst the most abundant and bioactive polyphenols in the human diet. IPEC‐1 cells are a non‐transformed, non‐tumorigenic cell line derived from pig ileum commonly used as a model to evaluate intestinal epithelial cell activity in vitro. In the present work, IPEC‐1 cells were used to determine the effect of proanthocyanidins on immune and inflammatory gene expression. Cells were treated with highly purified proanthocyandin extracts from cranberry and grape seed under non‐stimulated and LPS‐stimulated conditions during a 48 h total incubation period at 37°C. Inflammatory gene expression levels for ICAM‐1, CCL28, IL‐8, TLR4, TNF‐α, IL‐25, IL‐6, CCL20, MUC‐2, IL12p40, CCL2 (MCP‐1), and PTGS2 (COX‐2) were analyzed by real‐time RTPCR, and IL‐8 protein production in cell supernatants was determined by ELISA. Our results showed no significant change in cell viability or apoptosis, but ICAM‐1, CCL20, and IL‐8 gene expression was up‐regulated in response to proanthocyanidin extracts. Increased protein levels of IL‐8 were consistent with increased gene expression. Our results suggested that proanthocyanidins stimulate components of the inflammatory response of IPEC‐1 cells. This effect might be beneficial for certain immune‐related diseases. Funded by the Spanish MICINN (AGL2010‐17499) and ARS #1235‐51530‐053.