The influence of urethane and pentobarbital anesthesia on the pharmacokinetics of cefazolin has been investigated in rats. No significant difference of total body clearance or distribution volume was observed between urethane-anesthetized and non-anesthetized rats. There was also no significant difference in plasma concentration of cefazolin at the terminal phase between urethane-anesthetized, pentobarbital-anesthetized and non-anesthetized rats. Good coincidence was demonstrated between the observed tissue-to-plasma partition coefficient, K_p, of non-anesthetized rats and the predicted K_p value based on the previously proposed model. Hence, it is considered that there is no significant influence of urethane or pentobarbital anesthesia on the distribution and elimination of cefazolin. The proposed physiological model could be useful to predict the distribution of cefazolin in non-anesthetized rats.