Endogenous hypothalamic pro-inflammatory cytokines modulate the hypothalamic-pituitary-adrenal (HPA) axis responses. To investigate whether hypothalamic IL-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) are associated with differential inflammatory susceptibilities between Lewis (LEW/N) and Fischer (F344/N) rats, mRNA levels of pro-inflammatory cytokines and related molecules in hypothalamic cell cultures of both strains were quantified by real-time polymerase chain reaction (PCR). In addition to IL-1beta, IL-6, TNF-alpha, and their receptors, LEW/N hypothalamic cells also transcribed more anti-inflammatory molecules, IL-1RII, IL-1RA, and transforming growth factor (TGFbeta1), than F334/N cells. Our findings suggest that a balance exists between transcripts for endogenous pro- and anti-inflammatory molecules in LEW/N rats that may allow them, under basal conditions, to maintain hypothalamic homeostasis and health. However, under stimulated conditions, this balance may be more easily perturbed toward chronic inflammation.