Ageing is an important determinant of atherosclerosis development rate, mainly by the creation of a chronic low-grade inflammation. Diet, and particularly its fat content, modulates the inflammatory response in the fasting and postprandial states. Our aim was to study the effects of dietary fat on the expression of genes related to inflammation (NF-κB, monocyte chemoattractant protein 1 (MCP-1), TNF-α and IL-6) and plaque stability (matrix metalloproteinase 9, MMP-9) during the postprandial state of twenty healthy, elderly people who followed three diets for 3 weeks each: (1) Mediterranean diet (Med Diet) enriched in MUFA with virgin olive oil; (2) SFA-rich diet; and (3) low-fat, high-carbohydrate diet enriched in n-3 PUFA (CHO-PUFA diet) by a randomised crossover design. At the end of each period, after a 12-h fast, the subjects received a breakfast with a composition similar to the one when the dietary period ended. In the fasting state, the Med Diet consumption induced a lower gene expression of the p65 subunit of NF-κB compared with the SFA-rich diet (P = 0·019). The ingestion of the Med Diet induced a lower gene postprandial expression of p65 (P = 0·033), MCP-1 (P = 0·0229) and MMP-9 (P = 0·041) compared with the SFA-rich diet, and a lower gene postprandial expression of p65 (P = 0·027) and TNF-α (P = 0·047) compared with the CHO-PUFA diet. Direct plasma quantification mostly reproduced the findings. Our data suggest that consumption of a Med Diet reduces the postprandial inflammatory response in mononuclear cells compared with the SFA-rich and CHO-PUFA diets in elderly people. These findings may be partly responsible for the lower CVD risk found in populations with a high adherence to the Med Diet.