Objective To investigate the relationships between plasma secreted frizzled-related protein (SFRP) 5 level with type 2 diabetes (T2DM ) and carotid atherosclerosis (CAS). Methods According to the results of carotid color Doppler ultrasound ,56 T2DM patients were divided into 28 with carotid atherosclerosis (CAS group) and 28 without carotid atherosclerosis (NAS group). 28 healthy volunteers served as normal control (NC group). Serum SFRP5 was measured by ELISA. Results The level of serum SFRP5 in T2DM patients was lower than NC group (114.36 ± 25.48) vs (48.19 ± 11.82) , (43.88 ± 8.19)pg/ml ,(P<0.01). The difference of serum SFRP5 between CAS and NAS group shared no statistical significance [CAS (43.88 ± 8.19 ) vs NAS (48.19 ± 11.82 )pg/ml ,P> 0.05 ]. Pearson correlation analysis showed that serum SFRP5 was negatively correlated with age ,TG ,hsC-RP ,FPG ,FIns , HOMA-IR ,HbA1c ,TC ,LDL-C and BMI (P<0.01) ,and positively correlated with HDL-C (P<0.01). There were no significant correlations between SFRP5 and gender ,TC ,systolic blood pressure (SBP) and diastolic blood pressure (DBP) (P>0.05). Multiple linear regression results showed that age ,FIns and HbA1 c were independent influencing factors of serum SFRP5. Conclusion SFRP5 may be a protective factor for T2DM by ameliorating insulin resistance which may provide a new clue for the prevention and treatment of T 2DM.