The aim of the present study was to evaluate the bioavailability of a drug from rapidly disintegrating tablets prepared using fine spherical crystalline cellulose (PH-M-06®) and spherical sugar granules (Nonpareil®, NP). Rapidly disintegrating tablets containing acetaminophen as the model drug in combination with a mixture of NP-108 (purified D-mannitol) and PH-M-06 were prepared. Plasma concentration profiles and pharmacokinetic parameters of acetaminophen in rabbits were investigated after oral administration of the prepared tablets. No significant difference in C_max and AUC_0-∞ of acetaminophen between rapidly disintegrating tablets and conventional tablets was observed after direct administration of these tablets into the stomach of rabbits. However, t_max (15 min) of acetaminophen from rapidly disintegrating tablets was significantly (p<0.05) shorter than that from conventional tablets (130 min). The same t_max was observed for rapidly disintegrating tablets and solution. When suitable excipients such as fine spherical microcrystalline cellulose (PH-M series) and spherical sugar granules (NP series) were used, rapidly disintegrating tablets could be prepared by the conventional direct compression method. According to the results of moment analysis, the mean residence time (MRT) obtained between both rapidly disintegrating and conventional tablets indicates that the mean absorption time (MAT) from these tablets is approximately 60 and 90 min, respectively. This difference in MAT between the two tablets may be caused by the difference in the sum of the mean dissolution time (MDT) and the mean disintegration time (MDIT) of these tablets. Rapidly disintegrating tablets allow rapid absorption of the drug compared with conventional tablets.