Little is known about changes in the immune cell network that underlie pro-inflammatory cytokine elaboration in chronic heart failure (HF). Dendritic cells (DCs) and macrophages are antigen-presenting cells that play a central role in inflammation and immune tolerance. We investigated the pattern of infiltrating cardiac DCs and macrophages in chronic post-ischemic HF. Myocardial infarction (MI) was induced by left coronary ligation in male C57BL/6 mice. Pathological remodeling and HF were confirmed by hemodynamics, gravimetry, and echocardiography at 8 weeks post-MI. Sham-operated mice served as controls. At 8 weeks, cardiac infiltrating immune cells were isolated by collagenase digestion followed by density gradient centrifugation. Trypan blue-negative viable cells were quantified using flow cytometry. DCs were characterized using specific markers for classical (cDC) (CD11C+B220-), plasmacytoid (pDC) (CD11C+B220+), and immunogenic (CD11c+B220+CD86hi) and tolerogenic (CD11c+B220+CD86low) DCs. Macrophages were classified as activated (CD11b+F480+), pro- or anti-inflammatory (CD11b+F480+Gr1hi or low), and M1 (CD11b+F480+CD206-) or M2 (CD11b+F480+CD206+). Significant increases in cDCs (1.4 fold; p=0.016) and pDCs (4.3 fold; p=0.0016) were observed in failing myocardium. Surface expression of the maturation marker CD86 was increased 8.6 fold (p=0.009), whereas immature DCs exhibited a robust 24.4 fold (p=0.0005) increase. Activated macrophages were also significantly elevated in the failing heart as compared with sham-operated hearts (19.2 ± 1.9 vs 10.9 ± 2.9%; p=0.033), with marked infiltration of pro-inflammatory and M1 macrophages (6.2 ± 0.6 vs 3.8 ± 0.7%; p=0.019). In contrast, levels of anti-inflammatory and M2 macrophages were unchanged. We conclude that in chronic HF, there is marked upregulation of cDC and pDC subsets and pro-inflammatory/M1 macrophages that alter immune homeostasis, contribute to the recruitment and activation of immune cells, and underlie the chronic Th1 response in failing myocardium that promotes pathological remodeling. This suggests that targeting or altering immune cell subsets in the failing heart, rather than specific cytokines, may be a better approach to modulating inflammation in HF.