Abstract: In order to study the dissolution of nicotine in gum-based smokeless tobacco products in human buccal cavity, a novel buccal cavity simulator was developed and a method for simulating the in vitro release of nicotine was established. According to the amount of human nicotine release data from commercial gum-based chewing tobacco, the simulated dissolution parameters, including the chewing force, chewing frequency and the amount of saliva were determined for the simulator. The in vitro dissolution kinetics of nicotine in several typical gum-based chewing tobacco products of different formulas and manufacturing processes were investigated. The results indicated that:1) The simulator could well model the in vivo dissolution of nicotine in gum-based chewing tobacco. 2) The dissolution rate of nicotine in gum-based chewing tobacco was higher at first, and then became lower; it reached about 80% of contained nicotine after chewing for 15 min. 3) At initial dissolution stage, the coating of gum-based chewing tobacco postponed the in vitro release. 4) The dissolution rate of nicotine tartrate salt was much lower than that of ultrafine tobacco powder within first 8 min, as was the total dissolution rate. The results suggested that nicotine tartrate salt had a slowing effect on nicotine. This method provides a technical means to assess the manufacture and quality of gum-based chewing tobacco.