Objective To evaluate if expression of serum retinol-binding protein 4 (RBP4) concentrations in cholesterol gallstone disease.Methods Serum RBP4 levels of 100 cholesterol gallstone disease patients (cholesterol gallstone disease group) and 147 healthy controls (healthy control group) were measured by enzyme-linked immunosorbent assay and further correlated with clinical and biochemical characteristics,including insulin resistance and renal function.The chemical composition of gallstones was determined by postoperative pathology.Results The level of RBP4 in cholesterol gallstone disease group was significantly lower than that in healthy control group [(30.57 ± 13.64 ) mg/L vs.(41.52 ± 20.25 ) mg/L](P＜ 0.01 ).The level of RBP4 was also associated with gallstone occurrence (OR =0.93,95％ CI:0.88 -0.96,P =0.004).Serum RBP4 levels of all subjects were positively correlated with total cholesterol,triglyceride,creatinine,insulin resistance and albumin ( P ＜ 0.05 or ＜ 0.01 ),and negatively correlated with aspartate aminotransferase (P ＜0.01).In multivariate analysis,cholesterol gallstone formation was significantly associated with a lower serum RBP4 level (OR =2.97,95％ CI:1.15 -7.68,P =0.025 ).Both gallstone patients and controls were subdivided into two groups according to ceatinine:≥ 88.40 μ mol/L group and ＜ 88.40 μ mol/L group.Patients with gallstones were found to have significantly lower serum RBP4 levels than controls in both subgroups (P =0.012,0.045 ).According to GFR,both gallstone patients and controls were subdivided into ≥ 90 ml/(min· 1.73 m2) group,60 - 89 ml/(min· 1.73 m2) group and ＜60 ml/ (min· 1.73 m2) group.It showed that a lower GFR was associated with greater serum RBP4 level in healthy control group.This trend was not noted in cholesterol gallstone disease group.Conclusions Serum RBP4 decreases in cholesterol gallstone disease independent of renal function.The relationship between liver function and RBP4 level in these patients deserves further investigation.