Objective. The exact mechanisms that lead to RBC deformability and shape changes after trauma/hemorrhagic shock remain unknown. We hypothesize that RBC injury is caused in part by gut injury and is mediated by gut-derived factors carried in the intestinal lymph. Materials and methods. RBC deformability was measured by a laser-assisted ektacytometer before and after trauma/hemorrhagic shock (T/HS) in 6 rats whose mesenteric lymph duct had been ligated and in 10 rats subjected to T/HS without duct ligation. In this assay a decrease in the elongation index is a marker of decreased RBC deformability. RBC shape was examined by scanning electron microscopy. Results. In the T/HS rats, the RBC elongation index decreased after T/HS from a preshock value of 0.064 ± 0.011 to 0.052 ± 0.009 ( P < 0.01) and remained low (0.049 ± 0.010) even at 3 h after resuscitation. In contrast, the elongation index did not decrease after T/HS in the lymph duct-ligated rats (0.062 ± 0.004 vs. 0.056 ± 0.005, P = NS). Likewise, the T/HS rats, but not the duct-ligated T/HS rats, had a significant increase in the percentage of abnormally shaped RBCs when studied by electron microscopy. Conclusions. Interruption of lymph flow from the gut into the bloodstream by lymph duct ligation prevents T/HS-induced RBC damage. Because decreased RBC deformability contributes to impaired perfusion of the microcirculation, preservation of RBC deformability may decrease the incidence of T/HS-induced organ dysfunction.