Background/Purpose: Intestinal ischemia-reperfusion (IIR) induced acute lung injury (ALI) has been documented. Kupffer cell blockage with gadolinium chloride (GdCl3) has been shown to attenuate IIR-induced ALI. However, the effects of splenic monocytes/macrophages on IIR-induced ALI has not been studied previously. In the current study, the authors aimed to investigate the role of splenectomy in IIR-induced ALI. Methods: Forty-eight rats were divided randomly into 6 groups as follows: SHAM, SHAM + KCB, SHAM + SPLN, IIR, IIR + KCB, IIR + SPLN. Two hours of ischemia and 1 hour of reperfusion has been applied by clipping the SMA. GdCl3 was given 24 hours before experiment. Splenectomy was done just before SMA clipping. Lung levels of tumor necrosis-factor (TNF), interleukin (IL)-6, myeloperoxidase (MPO), and malondialdehyde (MDA) were assayed biochemically. Lung leukosequestration was determined by counting PMNLs histologically. Kruskal-Wallis and Mann-Whitney U tests were done; P values less than .003 were considered significant. Results: Polimorphonuclear leukocyte (PMNL) counts and biochemical parameters in the IIR group were significantly higher than the other groups (P < .003). When compared with IIR group, PMNL counts and biochemical parameters were significantly decreased in the IIR+KCB and IIR+SPLN groups, respectively (P < .003). However, they were still significantly higher than their sham-operated controls (P < .003). Conclusions: This study documents that splenectomy attenuates ALI as well as Kupffer cell blockage. Spleen, an important component of mononuclear phagocytic system as liver Kupffer cells, might play an important role in the IIR-induced ALI. © 2003 Elsevier Inc. All rights reserved.