The effectiveness of polyethylene glycol (PEG) based low volume resuscitation (LVR) solutions is dependent on polymer size,which correlated with their distribution in the microcirculation. Shocked rats resuscitated with PEG-20k all survived 24 hours(100 percent) compared to saline volume controls (0 percent) and had brain function scores comparable to sham controls after recovery from shock. PEG-20k was mainly excreted by the kidneys with a half-life of about 6 hrs. Maximum PEG-20k blood levels (3mg/ml) were 3 times lower than the lowest dose that produced a mild coagulopathy in ex-vivo blood testing using TEG in volunteers or trauma patients (10 mg/ml). Further coagulation and platelet function studies suggest the mild coagulopathy with higher doses of PEG LVR solutions is due to nonspecific platelet passivation to produce a slight thrombasthenia with very mild effects on fXIII induced fibrin cross bridging (at 10 mg/ml). In acute swine with lethal hemorrhage, LVR using PEG-20k significantly increased survival to the 4 hrs post-reperfusion end point with normal blood pressure and lactate. Resuscitation with equal volumes of LR, Hextend, or autologous whole blood showed much worse outcomes. All pigs died within 90minutes with very high lactates and lethal hypotension. Twenty-four hour survival was 100 percent in PEG20k treated swine and 0 percent in Hextend or whole blood. Survivors had normal lactate and neurological function scores.