Spermatogenesis is a highly controlled process of proliferation, meiosis, and differentiation. Systemic infection and chronic inflammation can impair testicular steroidogenesis and spermatogenesis. In this study, we examined the effect of systemic infection--intraperitoneal (i.p.) injection of lipopolysaccharide (LPS)--on the expression levels of IL-6 in the testis of sexually immature and adult mice. IL-6 levels in testicular homogenates of immature mice were significantly higher than in mature mice (both protein and RNA levels), before and after LPS injection. Injection of LPS (i.p.) into mature mice over 3 hours, significantly increased testicular IL-6 protein and mRNA levels (as demonstrated by ELISA and RT-PCR respectively) compared to the control group. Injection of LPS over 24 hours significantly increased IL-6 mRNA expression, but it did not significantly affect IL-6 protein levels in the homogenates. In contrast, stimulation of immature mice with LPS (2, 20 or 100 microg/mL) over 3 hours or LPS (2 or 20 microg/mL) over 24 hours, significantly increased testicular IL-6 (both protein and mRNA expression). The levels of testicular IL-6 (protein) in the homogenates were not significantly increased after stimulation with 100 microg/mL over 24 hours, but they were significantly increased at the mRNA level. Our results demonstrate, for the first time, the over-expression of IL-6 in testicular homogenates of mature and immature mice following systemic inflammation (i.p. injection of LPS). These results suggest the possibility of the involvement of systemic infection/inflammation, through the elevation of testicular IL-6, in testicular functions, which may affect male fertility. Also, high levels of IL-6 during pathological conditions, could play a role in protecting testicular tissue.