The type of diet consumed by individuals has been associated with the development of some chronic diseases, including cardiovascular disease (CVD), cancer, diabetes, and others. Populations that consume diets rich in fruits and vegetables and drink wine in moderation, as the Mediterranean, have a higher life expectancy and less chronic diseases than other occidental populations. We carried out an intervention study in humans to evaluate the effect of a Mediterranean diet (MD), an Occidental diet (OD) and their supplementation with red wine, on biochemical, physiological and clinical parameters related to atherosclerosis and other chronic diseases. For 3 months, two groups of 21 male volunteers each, received either a MD or an OD; during the second month, red wine was added isocalorically, 240 ml/day. At days 0, 30, 60 and 90, clinical, physiological and biochemical evaluations were made. In this article we report on the results obtained in plasma fatty acids profile that includes saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), omega-6 fatty acids, omega-3 fatty acids and omega-6/omega-3 ratio. Other results have been published previously. Plasma fatty acid percentages in the OD group, compared to the MD group, did not show differences in SFA, but the OD group showed lower levels of MUFA and omega-3 fatty acids, and higher levels of PUFA and omega-6 fatty acids, with a higher omega-6/omega-3 ratio than the MD group. Wine supplementation reduced MUFA and increased PUFA in both dietary groups, suggesting that wine could improve a diet with a good omega-6/omega-3 ratio. Volunteers on MD showed a better fatty acid profile than those on OD, suggesting a lower cardiovascular risk. Moderate consumption of wine improves this profile in the MD group.