Objective To investigate the change in serum preptin level and its association with insulin resistance( IR) in patients with nonalcoholic fatty liver disease( NAFLD). Methods A total of 72 patients with NAFLD who visited the outpatient service or were hospitalized in Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine and Dongfang Hospital Affiliated to Tongji University from April to August,2014 were enrolled,and 53 normal controls( NCs) matched by age and sex were also enrolled. All the subjects underwent ultrasound examination,and according to the results of ultrasound examination,the patients were divided into mild,moderate,and severe NAFLD groups. The following parameters were measured: body height,body weight,systolic blood pressure,diastolic blood pressure,waist circumference,hip circumference,liver function parameters,blood lipids,high- sensitivity C- reactive protein,fasting blood glucose,fasting insulin( FINS),glycosylated hemoglobin,and serum preptin level. Body mass index( BMI),waist- hip ratio,and homeostasis model assessment of insulin resistance( HOMA- IR) were calculated. The two- independent- samples t test was used to compare means of continuous data between groups,comparison between group was made by analysis of variance,and multiple comparisons were made by SNK- q test; and the Pearson correlation coefficient method was used for correlation analysis; a multivariate linear regression analysis was used to identify the the correlations between preptin and variables,and a logistic regression analysis was used to identify the associations between variables and NAFLD. Results The NAFLD patients had a significant increase in the preptin level compared with the control group( 385. 54 ± 72. 78 pg/ml vs 303. 85 ± 57. 54 pg/ml,t =- 6. 76,P < 0. 001); the mild,moderate,and severe NAFLD groups showed gradual increases and significant differences in the preptin level( 328. 58 ± 53. 51 pg/ml,376. 71 ± 57. 77 pg/ml,and 449. 35 ± 56. 95 pg/ml,respectively,P < 0. 001).The Pearson correlation analysis showed that serum preptin level was positively correlated with BMI( r = 0. 475,P < 0. 001),HOMA- IR( r =0. 671,P < 0. 001),and FINS( r = 0. 763,P < 0. 001). The multivariate linear regression analysis showed that FINS and HOMA- IR were independent influencing factors for serum preptin level. The logistic regression analysis showed that preptin was closely associated with NAFLD. Conclusion Preptin is closely associated with the development of NAFLD and may be involved in the development and progression of NAFLD by affecting insulin resistance.