Background: C1q/TNF-Related Protein (CTRP) family members are novel adipokines that have immunomodulatory, anti-inflammatory, glucose regulating, and vascular effects. However, their microvascular effects in diabetic patients remain unclear. Objective: To evaluate the relation between serum CTRP9 and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Patients and Methods: This cross-sectional study was conducted on 90 subjects with their ages ranging from 35-70 years, selected from diabetes and ophthalmology outpatient clinics of Ain shams University Hospitals for 6 months in a period from May 2019 to November 2019. They were divided into 3 groups: Group (I): 35 Patients with T2DM with diabetic retinopathy. Group (II): 35 Patients with T2DM without diabetic retinopathy. Group (III): 20 Apparently healthy individuals. Results: there is a highly statistically significant difference between the studied groups as regards S. CTRP9 being highest in Group II Patients with T2DM without diabetic retinopathy followed by Group III Apparently healthy individuals then Group I Patients with T2DM with diabetic retinopathy (P-value <0.001). Also, there is a negative correlation between serum CTRP9 level and Duration of DM, HbA1C FBS, and 2hpp. On performing multiple linear stepwise regression analysis to the statistically significant factors using CTRP9 as a dependent variable with other independent variables, only HbA1C and Duration of DM remained significantly associated with CTRP9. Conclusion: T2DM patients with diabetic retinopathy have decreased CTRP9 levels regardless of the grade of retinopathy. Loss of protective role of CTRP9 may attribute to DR in patients with long-standing Diabetes.