Objective: To investigate the role of leptin in gallbladder cholesterol stone formation through analysing the relations of leptin with gallbladder bile components and blood lipids in patients with gallbladder cholesterol stones. Methods: Thirty patients with gallbladder cholesterol stones undergoing elective laparoscopic cholecystectomy (gallstone group) and 22 patients undergoing elective laparoscopic cholecystectomy for gallbladder polyps (polyp group) during the same period were selected. In these patients, the serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and leptin as well as the concentrations of bile TC and total bile acid (TBA) in gallbladder and the mRNA expression of leptin receptor in the tissues of gallbladder wall were determined. Results: In gallstone group compared with polyp group, the serum levels of TC, TG, LDL and leptin as well as the bile TC/TBA ratio in the gallbladder and mRNA expression level of leptin receptor in the gallbladder tissue were all significantly increased, while the serum level of HDL was significantly decreased (all P<0.05). In gallstone group, the serum leptin level had significantly positive correlation with serum TG and TC levels and bile TC content (r=0.633, P=0.002; r=0.224, P=0.025; r=0.384, P=0.000), and significant negative correlation with HDL level and TBA content (r=-0.205, P=0.014; r=-0.548, P=0.024); in polyp group, the serum leptin level showed no significant correlation with all above variables (all P>0.05). Conclusion: Leptin participates in gallbladder cholesterol stone formation. The increased levels of leptin and its receptor may be closely related to abnormal cholesterol metabolism and gallbladder bile component imbalance.