Abstract Body: Background: Particulate matter (PM) exposure triggers a lung-mediated inflammatory response via monocyte chemoattractant protein-1 (MCP-1) that reduces cardiomyocyte function in vitro. Hypothesis: We hypothesized that knockout of the MCP-1 receptor, C-C chemokine receptor type 2 (CCR2), would preserve cardiac function during long-term whole-body ambient PM exposure. Methods: Male C57BL/6 control (Con) and CCR2^-/- mice were exposed to filtered air (FA) or ambient PM for 9-months (6 h/d, 5 d/week; Con: 24 h avg. = 20.46 μg●m^-3; CCR2^-/-: 24h avg. = 20.63 μg●m^-3). Left heart structure and function were assessed via echocardiography and cardiac pressure-volume (PV) loops, and sarcomere function was evaluated in isolated cardiomyocytes under regular conditions and with isoproterenol (100 nM). Data were analyzed via two-way ANOVA. Multiple comparisons were adjusted with Sidak’s test between exposure and genotype. Data reported as means with 95% CI’s. Results: Echocardiography revealed that left heart structure and function were similar between exposures and genotypes (all p > 0.05); however, PV loop analysis showed PM reduced end-systolic elastance, an effect exacerbated in CCR2^-/- (CCR2^-/-: 1.3 [0.7, 1.9] vs Con: 1.8 [1.5, 2.2] mmHg●µL^-1 vs], p = 0.06). CCR2^-/- cardiomyocyte function was preserved following PM although slightly lower FA contraction (CCR2^-/-: -1.6 [-1.8, -1.4] vs Con: -1.9 [-2.3, -1.5] µm●s^-1, p = 0.08) and relaxation velocities (CCR2^-/-: 1.0 [0.9, 1.2] vs Con: 1.4 [0.9, 1.8] µm●s^-1, p = 0.08 may have contributed. When treated with isoproterenol, PM cardiomyocytes had reduced contraction and relaxation velocities in CCR2^-/- (-1.7 [-2.2, -1.1] µm●s^-1, p < 0.01 and 1.0 [0.5, 1.4] µm●s^-1, p < 0.01), along with slower time to 90% peak shortening (0.08 [0.07, 0.09] s, p < 0.01) and peak relaxation (0.34 [0.23, 0.45] s, p < 0.01) compared to cells from FA. No differences in intracellular calcium amplitude (Δ 340/380) or kinetics (tau) were detected between genotypes under regular conditions but were similarly increased with isoproterenol. Conclusion: Contrary to our hypothesis, CCR2 supports the normal cardiovascular adaptation to long-term particulate matter exposure and may confer cardiac resilience, particularly under adrenergic stress.