In this study, the isolated use of methylene blue (MB) in the treatment of anaphylactic shock induced by Compound 48/80 (C48/80), a potent histamine releaser, was examined, and the study of the effects of MB on the function of the aorta artery endothelium was accomplished in vitro. MB was used in a single 3.0 mg/kg dose, and C48/80 was used in a single 4.5 mg/kg dose. The study protocol included the following experimental groups, containing six animals each: group I (control), animals in the absence of any drug action; group II (MB), MB infusion; Group III (C48/80), anaphylactic shock induced by using C48/80; group IV (C48/80+ MB), anaphylactic shock treated with MB infusion at the moment of major hypotension; and group V (MB+ C48/80), prevention of anaphylactic shock with MB by means of MB infusion minutes before the 4.5 mg/kg C48/80 infusion. Nitric oxide plasma levels were measured in each of the experimental groups. After the in vivo studies were performed, an in vitro study was conducted using segments of the abdominal aortas of the rabbits to determine the effect of MB on the arterial endothelium. The results obtained in the present investigation have shown that MB intravenous infusion does not change the mean arterial pressure when compared with the control group (n= 6 in each group, P< 0.05); that C48/80 is effective in producing experimental anaphylactic shock (n= 6, P< 0.05); that the attempt to prevent anaphylactic shock with MB results in a mean prolongation of animal survival ranging from 17 to 34 min (n= 6 in each group, P< 0.05); that MB is effective in reversing anaphylactic shock in all the studied rabbits (n= 6, P< 0.05); that absolute and percentage plasma nitrate values obtained with the experimental groups do not differ (n= 6, each group, P< 0.05); and that the in vitro study of segments of abdominal aorta has shown that there has not been endothelial dysfunction in any of the groups (n= 6 in each group, P< 0.05). The good results obtained in this study open a research path that may offer data to define new paradigms for treating anaphylaxis.