The main objective of this study was to investigate the release and pharmacokinetic profiles of ketoprofen (KP) from developed thermosensitive and mucoadhesive liquid suppositories. Thermosensitive liquid suppositories were prepared using KP, poloxamer 407 (P 407), poloxamer 188 (P 188) and various amounts of different mucoadhesive polymers. In vitro release studies was monitored by the USP XXVI paddle method. The results thus obtained were evaluated kinetically and mechanism of release was analyzed. Identification of poloxamer gel localization in vivo was conducted using white male rabbits by adding 1 % methylene blue. For in vivo studies, twenty-four white male rabbits were randomly divided into three groups. The rabbits in each group were administered with liquid suppository F1 [P407/P188/KP (4/20/2.5 %)], F5 [P407/P188/KP/C (4/20/2.5/0.8 %)] or conventional suppository (F-C) into the rectum. The plasma concentration of KP was analyzed by high performance liquid chromatography (HPLC). C (max), AUC, MRT and T (max) were evaluated. The release of KP was variously affected by the mucoadhesive polymers. In vitro release studies showed that Carbopol 934 P(C) has significant effect on release rate among the mucoadhesive polymers. When the formulations were evaluated kinetically, different kinetic models were obtained. Formulation F6 [P407/P188/KP/C (4/20/2.5/1.6 %)] which contains the highest C concentration and very high viscosity, shows a significantly better fit with Higuchi kinetic model. n value of this formulation was also found approximately 0.5. n exponent results of the other formulations showed that KP might be released from the suppositories by non-Fickian diffusion. Identification of poloxamer gel localization in vivo showed that the suppositories remain in the rectum without leakage after administration. With regard to the results of in vivo studies, the AUC(6 -> 14) values of KP in liquid suppository containing C are significantly higher than those in liquid suppository without C. MRT0 -> 24 and MRT0 -> a values of liquid suppository containing C are significantly higher than those in liquid suppository without C and conventional suppository. Conventional suppository and liquid suppository without C significantly gave faster time to reach the maximum plasma concentrations of KP. With regard to the in vitro and in vivo experiments, liquid suppository formulation F5 might be a promising formulation for the development of an effective rectal dosage form.