Abstract: Objective Detect the serum lipids, leptin and cholecystokinin (CCK) before/after the minimally invasive surgery of gallbladder-preserving cholecystolithotomy (MISGPC), to reveal the variations and discuss the relations between the variations and the postoperative recurrence of gallstones. Methods Choose 30 patients who underwent the MISGPC for the research group (RG) and 30 healthy persons for the normal control group (NCG). Detect the concentrations of the serum lipids, leptin and CCK before/after the MISGPC, analyze the diversity, and compare with the NCG. Results The postoperative concentrations of HDL, leptin and CCK are lower than the preoperative levels (P = 0.00, 0.000, 0.000), the levels of TC, TG and LDL are no differences between pre and post operation (P = 0.068, 0.873, 0.097). The preoperative concentrations of TG, leptin and CCK are higher than the NCG (P = 0.025, 0.002, 0.000), the levels of TCH, LDL and HDL are no differences between the preoperative RG and the NCG (P = 0.842, 0.846, 0.330). The postoperative concentrations of TG and CCK are higher than the NCG (P = 0.009, 0.005), the postoperative level of HDL is low than the NCG (P = 0.000), the levels of TCH, LDL and leptin are no differences between postoperative RG and the NCG (P = 0.312, 0.384, 0.952). Conclusions The concentrations of serum leptin and CCK are significantly reduced after the MISGPC, this fact is very meaningful for preventing the recurrence of gallstones after surgery. The concentration of HDL is reduced postoperatively, but the levels of TCH, TG and LDL do not vary significantly, this indicates that low fat diet and physical training are very important to prevent the recurrence of gallstones after the MISGPC.