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Abstract: Objectives: Proinflammatory cytokines, matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in left ventricular (LV) structural remodeling. We aimed to investigate the effects of cardiac resynchronization therapy (CRT) on serum levels of amino-terminal prohormone B-type natriuretic peptide (NT-proBNP), some interleukins (IL-1β, IL-6, IL-8), MMP-2 and TIMP-2 in patients with chronic heart failure (CHF). Design and methods: We studied 27 patients (15 M/12 F) with CHF, III–IV NYHA class, implanted with a biventricular pacemaker/defibrillator and 40 healthy subjects (23 M/17 F). Blood samples were collected at baseline and 1week, 3, 6, and 12months after CRT device implantation. Cardiac function was assessed echocardiographically. Results: CRT induced significant improvement in the NYHA class (baseline 3.2±0.5 vs. 1.0 at 12months, P=0.0002) and significant LV reverse remodeling, with a 41% (P=0.001) reduction in LV end-systolic volume (LVESV). This was associated with a significant reduction in serum NT-proBNP, IL-6 and IL-8. Positive extracellular matrix remodeling was illustrated by decreasing levels of MMP-2 and increasing TIMP-2. MMP-2/TIMP-2 ratio decreased with 55% (P=0.003) from baseline value at 12months and the correlation with LVESV reduction was 0.41 (P=0.001). Conclusions: Structural response to CRT is associated with reduced immune activation and positive extracellular matrix remodeling. [Copyright &y& Elsevier]