Intestinal ischemia/reperfusion (I/R) causes local and remote injuries that are multifactorial and essentially inflammatory in nature. To study the putative influences of nitric oxide (NO) and tumor necrosis factor α (TNF-α) on the release of interleukin (IL) 1β and IL-10 and the involvement of lymphatic system on a systemic inflammation caused by I/R, we have quantified the serum and lymph levels of IL-1β and IL-10 in rats during I/R after treatment with inhibitors of NO synthase (N ω-nitro-L-arginine methyl ester hydrochloride [L-NAME]) or TNF-α (pentoxifylline [PTX]). Intestinal I/R was performed by means of a 45-min occlusion of the mesenteric artery, followed by 2-h reperfusion; groups of rats subjected to I/R had the thoracic lymph duct ligated immediately before the procedure. The I/R caused a significant increase of the serum levels of IL-1β and IL-10 in rats with intact thoracic lymph duct, whereas the thoracic duct ligation blunted the serum release of IL-1β and elevated that of IL-10. The levels of the cytokines collected in the lymph after I/R increased, and even more increase was observed in L-NAME-treated rats. L-NAME significantly increased the lymph levels of IL-1β and IL-10; in serum, however, only IL-1β increased in rats with either intact or ligated thoracic lymph duct. The treatment with PTX reduced the serum levels of IL-1β irrespective of the lymph circulation interruption but was effective to increase the IL-10 levels in intact rats during I/R. The lymphatic levels of IL-1β of rats subjected to I/R were reduced and those of IL-10 were increased after treatment with PTX. In conclusion, during I/R, the serum levels of IL-1β seem modulated by stimulant mechanisms that could be associated with TNF-α and inhibited by NO and by the integrity of the thoracic lymphatic flow. On the other hand, IL-10 seems controlled by TNF-α-related, largely NO-independent mechanisms. Thus, it is reasonable to suppose that an endogenous mechanism that can limit the systemic inflammatory response ensuing an I/R splanchnic trauma exists.