The xenobiotic absorption process is dependent on many factors, related both to the substance and form of its administration. During administration of small amounts of drugs, the effect of vehiculum on drug fate in the body becomes also evident. The intensity of absorption depends on numerous factors not necessarily related to the substance and its formulation, and also on biotransformation and active transport processes. Additional problem is the fact that many medicines are lipophilic compounds and insoluble in the water (e.g. phenacetin). Methanol and its aqueous solutions facilitate administration to the experimental animals, in the dissolved form of a number of medicines practically insoluble in water. Taking into consideration that methanol is particularly for rats, of low toxicity, it is quite frequently applied as vehiculum. The aim of this study was to investigate the potential interactions that may occur during the use of methanol as vehiculum and compare changes when were used solution 1% of carboxymethylcellulose. The study was performed on male Wistar rats. The tests were performed using phenacetin, which is recognized as biomarker of CYP 2E 1 isoform activity. Phenacetin was given per os in a single dose of 100 mg/kg b. w. Various procedures of phenacetin administration were tested, including solubilization in methanol or suspension in 1% water solution of carboxymethylcellulose. The results of this study show that methanol influences the phenacetin bioavailability and kinetics. Comparing the administration of this drug in methanol solutions against 1% of carboxymethylcellulose, it is in the case of phenacetin triple increase in AUC0-4 h. The presence of methanol affects the shape of kinetic curves of phenacetin causing higher their course until 4 hours after administration.