The purposes of the present study were to analyze liver inflammation and endothelial dysfunction in an experimental model of metabolic syndrome (MS) induced by chronic administration of a sucrose-rich diet (SRD) and to evaluate the effects of chia seed as a therapeutic strategy. Male Wistar rats were fed with a reference diet (RD) for 6 months or a SRD for 3 months. Then, the latter group was randomly divided into two subgroups. One subgroup continued receiving the SRD for up to 6 months and the other was fed with a SRD where whole chia seed was incorporated as a source of dietary fat for the next 3 months (SRD + CHIA). Results showed that rats fed a SRD for a long period of time developed dyslipidemia, hyperglycemia, inflammation and endothelial dysfunction. Hepatic NAS, IL-1β, NFκB p65, PAI-1, and F4-80 expression, as well as MPO activity were significantly increased and IL-10 expression was significantly decreased; this was accompanied by increased plasma IL-6 and TNF-α levels in rats fed a SRD. In addition, serum and liver nitric oxide (NO) levels and nitric oxide synthase (NOS) were significantly increased in the SRD group. In addition, a significant increase in hepatic iNOS expression and a positive correlation of this with liver NFκB p65 was found. We observed a significant increase in hepatic intercellular adhesion molecule (ICAM), and a negative correlation of this with liver Nrf2 was found. The administration of chia seed for 3 months reversed dyslipidemia, hyperglycemia, inflammation and endothelial dysfunction. In the liver tissue, NAS, IL-1β, IL-10, NFκB p65, PAI-1, and F4-80 expression and MPO activity were normalized. Serum and liver NO and NOS levels and hepatic iNOS expression were decreased and this last one was associated with a decrease in liver NFκB p65 levels. Hepatic ICAM-1 was normalized and negatively correlated with liver NrF2 levels. This study showed new aspects of liver inflammation and endothelial dysfunction in dyslipidemic insulin resistant rats chronically fed with a sucrose-rich diet. In addition, we demonstrated new properties and molecular mechanisms associated with beneficial effects on inflammation and endothelial dysfunction of chia seed as a therapeutic strategy.