Abstract: In this paper, progesterone was selected as a model drug and poloxamer 407 was selected as thermosensitive agent to prepare progesterone thermosensitive in situ gel. Selection of the moistening and bioadhesive agents, and the effects of the excipients on the gelation temperature were evaluated. In addition, the impacts of content of glycerol, paraffin liquid, labrafil, poloxamer 407 and different drug particle sizes on the drug release process were determined using a custom-made in vitro release device. In vitro release vs time profile was then mathematically modeled by zero order kinetic, first order kinetic and Higuchi equation, respectively. Glycerol was found to possess the best moistening effect, and polycarbophil had the strongest bioadhension. The optimal formulation consisted of 4. 0% progesterone, 20% poloxamer 407, 5. 0% glycerol, 5. 0% paraffin liquid, 2. 0% labrafil, 0. 2% polycarbophil, 0. 08% sorbic acid and 0. 1 mol/L citrate phosphate buffer(pH 4. 0), whose gelation temperature was 33. 8 °C. The in vitro release study indicated that the release rate was related to drug particle size, content of labrafil and paraffin liquid, and that release of progesterone was best fitted to first-order kinetics. Compared with common Carbomer gel, the thermosensitive gel obtained using this formula could promote the release of progesterone.