Inappropriate inflammation has been linked to stress-related psychiatric disorders such as depression, anxiety, and posttraumatic stress disorder (PTSD). Inflammation is associated with increased proinflammatory cytokines, such as interleukin 1 beta (IL-1β), interleukin 23 (IL-23), and interleukin 6 (IL-6). Increasing evidence suggests that the microbiome, particularly a category of microorganisms referred to as “old friends” is an important determinant of the balance between regulatory and effector T cell populations (i.e., immunoregulation). However, how these “old friends” are able to exert their immunoregulatory effects is not fully understood. Mycobacterium vaccae (M. vaccae), a saphrophytic mycobacterium, has been shown to have a protective effect on depressive- and anxiety-like behaviors in several animal models of stress. For example, M. vaccae has been shown to have stress resilience effects in male rats after exposure to inescapable tail shock stress (IS), as assessed by the juvenile social exploration (JSE) test, in a model of learned helplessness, but the mechanism of how it achieves these effects is not fully understood. Previous research using stress models such as repeated social defeat (RSD) have shown that anxiety- and depressive-like behaviors are associated with an increase of circulating Ly6Chi inflammatory monocytes in mice. One hypothesis is that M. vaccae may be exerting its effects in part through its interaction with these inflammatory monocytes. This experiment is a pilot study that characterized leukocyte subpopulations after IS in rats using a previously established nine-color immunophenotyping panel that identified neutrophils, inflammatory and anti-inflammatory monocytes, natural killer (NK) cells, B cells, and CD4+ and CD8+ T cells. Compared to home cage (HC) controls, IS increased neutrophils but decreased lymphocytes in the peripheral blood 6 hours after IS. Additionally, IS increased the relative proportion of inflammatory monocytes, suggesting that the stress-induced effects of IS may be due in part to the increase of the relative percentage of inflammatory monocytes. This study supports the hypothesis that inflammatory monocytes are involved in the pathogenesis of stress-induced anxiety-like defensive behavioral responses and corroborates with previous lines of research characterizing leukocyte subpopulations after stress.