This study examined the absorption and pharmacokinetic disposition of $^{125}I-GST-TatdMt$, a recombinant Tat protein possessing potent anti-obesity activity, in mice after vascular and extravascular administration. GST-TatdMt was over-expressed in E. coli, purified, and radioiodinated using the IODO-GEN method. $^{125}I-GST-TatdMt$ was administered to mice by i.v., i.p. and oral administration at doses of 652.7 nCi (102.3 ${mu}g$). Upon i.v. injection, the average terminal elimination half-life ($t_{1/2,{lambda}z}$), AUC and AUMC were 6.4 h, 318.2 $nCi{cdot}h/mL$ and 2518 $nCi{cdot}h^{2}/mL$, respectively. The highest radioactivity was observed in lung followed by liver, spleen, heart and kidney. The $t_{1/2,{lambda}z}$ values obtained from i.v., i.p., and oral administration were comparable from each other (range 5.8-6.4 h). The absolute bioavailability of $^{125}I-GST-TatdMt$ was 42.8% and 60.5% after p.o. and i.p. administration, respectively. Given the cell-penetrating nature, $^{125}I-GST-TatdMt$ may be absorbed into the systemic circulation to a relatively high extent after extravascular administration.