Macrophage and T cell infiltration into metabolic tissues contributes to obesity-associated inflammation and insulin resistance (IR). C-C Chemokine Receptor 5 (CCR5), expressed on macrophages and T cells, plays a critical role in the recruitment and activation of pro-inflammatory M1 and T_H1 immune cells to tissues and is elevated in adipose tissue (AT) and liver of obese humans and mice. Thus, we hypothesized that deficiency of CCR5 would protect against diet-induced inflammation and IR. CCR5 deficient (CCR5^-/-) and C57BL/6 (WT) controls were fed 10% low fat (LF) or 60% high fat (HF) diets for 16 weeks. HF feeding increased adiposity, blood glucose, and plasma insulin levels equally in both genotypes. Opposing our hypothesis, HF-fed CCR5^-/- mice were significantly more glucose intolerant than WT mice. In AT, there was a significant reduction in the M1 associated gene, CD11c, while M2 associated genes were not different between genotypes. In addition, HF feeding caused a 2-fold increase in CD4⁺ T cells in the AT of CCR5^-/- compared to WT mice. In liver and muscle, no differences in immune cell infiltration or inflammatory cytokine expression were detected. However in AT and muscle, there was a mild reduction in insulin-induced phosphorylation of AKT and IRβ in CCR5^-/- compared to WT mice. These findings suggest that while CCR5 plays a minor role in regulating immune cell infiltration and inflammation in metabolic tissues, deficiency of CCR5 impairs systemic glucose tolerance as well as AT and muscle insulin signaling.