The present study was undertaken to investigate, if the non-steroidal anti-inflammatory drug (NSAID) piroxicam (CAS 36322-90-4) Fast-Dissolving Dosage Form (FDDF) can be absorbed in the oral mucosa. Piroxicam FDDF was administrated under the tongue to rats with an oesophagus ligation (OL) to prevent the drug entering the stomach and in turn its absorption by the classic way. A group of sham-operated (SO) animals received the same piroxicam FDDF dose. After drug administration, a pharmacokinetic study with serial serum sample extractions at 0, 15, 30, 60 and 120 min was performed. It has been found a prompt increase in serum piroxicam levels in OL-rats, which showed different pharmacokinetics from SO-rats. Areas under curve (AUCs) of OL-rat serum piroxicam levels were higher at 15, 30 and 60 min compared to SO-animals. These results indicate that piroxicam FDDF is absorbed in the rat oral mucosa. Moreover, during the first hour, drug absorption by oral mucosa rendered higher piroxicam levels than gastric absorption.