Anorexia nervosa (AN) is a serious eating disorder prevalently widespread in female subjects, characterized by a severe restriction of caloric intake, fear of becoming fat, dysmorphophobia and hyperactivity (DSM–5). Nowadays growing evidence shed light about the involvement of immunoinflammatory pathways in AN, considering the rise in the peripheral levels of pro-inflammatory cytokines in patients (Solmi et al., 2015). Furthermore, neuroinflammation may be an additional characteristic of AN (Rahimian et al., 2021), since it has been observed in other psychiatric disorders. The Activity-Based Anorexia (ABA) paradigm, which combines caloric restriction with physical activity, is the most frequently employed animal model which reproduces the primary characteristics of AN (Scherma et al., 2023). The aim of our study was to investigate, for the first time in ABA female rats, the mRNA expression of TNF-α, IL-6, IL-1β, NLRP3, and CD11B in the dorsal hippocampus and prefrontal cortex, and the microglial density in several brain regions implicated in AN. Our results show an overall reduction in the expression of proinflammatory markers, except for the increase of IL-6, an overall reduction was also found in the microglial density, evidenced by the immunostaining of IBA-1. Our findings suggest that combining caloric restriction and physical activity might have an initial protective role against neuroinflammation in ABA animals. However, our ABA model only represents the early, acute stages of AN. Further investigation after extended fasts and body weight recovery is required to better understand the role of neuroinflammation and evaluate new treatment options for AN in humans.