Immunological interventions in endotoxemia and sepsis have been tested in experimental and clinical studies. Our group evaluated the effects of an immunoglobulin (Ig)M-enriched solution in an established model of Gram-negative bacteraemia. Ten New Zealand White rabbits (2 - 3 kg) were randomized to a treatment or control group. In both groups, LPS was infused at a rate of 40 mg kg h. Immunoglobulin M-enriched solution (Pentaglobin; 2 mL kg h) was applied in the intervention group 15 min after beginning LPS infusion. 1 × 10 colony forming units of Escherichia coli were injected 30 min after LPS infusion was commenced. Baseline hemodynamic and respiratory parameters, blood E. coli concentration (30 min before and 1, 15, 30, 60, 90, 120, and 180 min after E. coli injection), polymorphonuclear neutrophil oxidative burst activity, and phagocytosis dead space (both 30 min before and 1, 15, 60, 120, and 180 min postinjection) were measured. Ex vivo phagocytosis activity was measured in a separate experiment and evaluated by electron microscopy. Diffuse alveolar damage (DAD) was measured. Organ colonization (kidney, lung, liver, spleen) was assessed in aseptic organ samples. Hemodynamic parameters did not differ between the two groups. Bacterial blood clearance was not influenced by application of IgM-enriched solution. Liver and spleen colonization was significantly reduced in the IgM group. Immunoglobulin M-enriched solution reduced in vitro residual phagocytosis capacity at 30, 90, and 180 min and improved respiratory burst at 180 min. Correspondingly, ex vivo phagocytosis activity as documented by electron microscopy was increased in the IgM group. The sum of all weighted DAD scores (except overdistension) was significantly better in the IgM group (23 ± 5 vs. 30 ± 8). Immunoglobulin M-enriched solution significantly improved six of seven DAD score parameters and reduced liver and spleen E. coli count. Residual phagocytosis capacity was significantly decreased in the IgM group, whereas burst activity was increased, pointing to an increased in vivo phagocytosis efficiency. Short-term IgM-enriched solution intervention had an especially beneficial effect on LPS-induced pulmonary histological changes.