Abstract Antidepressant-like effects of medium-chain fatty acid-containing dietary oil were examined by using mice forced to swim. This stress loading induced features typical for depression such as depressive symptoms and decreased the ratio of phosphorylated (p) extracellular signal-regulated kinases (ERK)1/2 to ERK1/2 in the hippocampus, demonstrating that our animal model prepared in mice was comparable to the general models using rats. Test diets containing structured medium- and long-chain triacylglycerols (MLCTs) and/or long-chain triacylglycerols (LCTs) as test oils and tap water were given freely during the stress period. Consequently, the intake of MLCTs resulted in a significant reduction in the immobility time in the forced swim test. Moreover, the ratio of pERK1/2 to ERK1/2 in the hippocampus was significantly higher in mice fed the MLCT diet than in those fed the LCT one. These results are the first evidence showing that MLCTs have a preventive effect against forced swimming-induced depression-like symptoms.