Background: In this study, we used Methotrexate (Mtx) to examine the role of immunomodulation on the activation of IL-6 and VCAM-1, which could generate a microenvironment that supports cardiovascular remodelling.Methods: Male WKY and SHR rats were separated into five groups: Control, FFR: WKY rats receiving a 10% (w/v) fructose solution during all 12 weeks, SHR, FFHR: SHR receiving a 10% (w/v) fructose solution during all 12 weeks and FFHR+Mtx (0,3 mg/kg intraperitoneal one injection per day week for 6 weeks) (n = 8 per group). Metabolic variables and systolic blood pressure were measured. Cardiac and vascular remodelling was also evaluated. To assess this, IL-6R and VCAM-1 immunostaining techniques were used.Results: The FFHR experimental model developed metabolic syndrome, vascular and cardiac remodelling, and vascular inflammation because of increased expression of IL-6 and VCAM-1. Chronic treatment with Mtx completely or partiality reversed the variables studied.Conclusions: The results demonstrated an impact on immunomodulation after mtx treatment, which included a reduction in vascular inflammation and a favourable reduction in metabolic and structural parameters.Fil: Renna, Nicolas Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Ramirez, Jésica M.. Universidad Nacional de Cuyo. Instituto de Genética; ArgentinaFil: García, Rodrigo Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Diez, Emiliano Raúl. Universidad Nacional de Cuyo. Instituto de Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Miatello, Roberto Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Instituto de Genética; Argentin