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Background: The purpose of the study was to determine whether the use of β-adrenoceptor antagonists (β-blockers) can affect metalloproteinase 2 (MMP-2) and its tissue inhibitor (TIMP-2) in patients with chronic kidney disease (CKD) on conservative treatment. Methods: The circulating MMP-2/TIMP-2 system, proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the marker of oxidative stress—Cu/Zn superoxide dismutase (Cu/Zn SOD)—were measured in 23 CKD patients treated with β-blockers [β-blockers (+)] and in 27 CKD patients not receiving the above medication [β-blockers (−)]. Results: The levels of MMP-2, TIMP-2, and IL-6 were significantly lower in the β-blockers (+) than in the β-blockers (−) group, whereas Cu/Zn SOD concentrations were not affected by β-blocker use. There was a strong, independent association between MMP-2 and TIMP-2 in both analyzed patient groups. In the β-blockers (+) group, MMP-2 levels were indirectly related to the signs of inflammation, whereas in the β-blockers (−) group, the alterations in the MMP-2/TIMP-2 system were associated with the oxidative stress marker and CKD etiology. Conclusions: This study is the first to suggest that the use of β-blockers was associated with the reduction in IL-6 and the MMP-2/TIMP-2 system in CKD, providing a pharmacological rationale for the use of β-blockers to reduce inflammation and abnormal vascular remodeling in CKD. [ABSTRACT FROM AUTHOR]