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The selection of the anesthetic regime is a crucial component in many experimental animal studies. In rodent models of liver disease, the combination of ketamine and diazepam (KD), generally by the intramuscular (i.m.) route, has traditionally been the anesthesia of choice for the evaluation of systemic and hepatic hemodynamics but it presents several problems. Here, we compared the performance of inhalational sevoflurane (Sevo) against the KD combination as the anesthesia used for hemodynamic studies involving the measurement of portal pressure in normal rats (Ctrl) and rats with non-cirrhotic portal hypertension induced by partial portal vein ligation (PPVL). Compared with Ctrl rats, rats with PPVL presented characteristic alterations that were not influenced by the anesthetic regime, which included liver atrophy, splenomegaly, increased plasma fibrinogen, decreased alkaline phosphatase and glycemia, and frequent ascites. The use of the KD combination presented several disadvantages compared with the inhalational anesthesia with sevoflurane, including considerable mortality, a higher need of dose adjustments to maintain an optimal depth of anesthesia, increases of heart rate, and alteration of blood biochemical parameters such as the concentration of aspartate aminotransferase, lactate, and lactic dehydrogenase. Rats anesthetized with sevoflurane, on the other hand, presented lower respiratory rates. Importantly, the anesthetic regime did not influence the measurement of portal pressure either in Ctrl or PPVL rats, with the increase of portal pressure being similar in Sevo- and KD- anesthetized groups of PPVL rats compared with their respective control groups. Overall, our results suggest that anesthesia with sevoflurane is preferable to the combination of KD for performing systemic and hepatic hemodynamic studies in rats with non-cirrhotic portal hypertension.