Abstract Background Diabetes mellitus is a heterogeneous metabolic disorder characterized by the presence of hyperglycemia which is associated with long-term micro-vascular complications affecting the eyes resulting in diabetic retinopathy (a leading cause of blindness). Pentraxin 3 (PTX3) is a recently discovered mediator of acute inflammation which has been shown to be a sensitive biomarker of localized inflammatory reactions with a possibility of being used as a biomarker of peripheral vascular damage. Objective To evaluate the relation between levels of plasma Pentraxin 3 (PTX3) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus. Methods This case control study was conducted on70 patients with type 2 DM and 20 healthy subjects as control and their ages ranged from 40-70 years, selected from outpatient diabetes and endocrinology clinic at El Demerdash Hospital/Ain-Shams University and outpatient diabetes and endocrinology clinic at National Institute of Diabetes and Endocrinology. The included subjects were allocated into three groups: Group I (type 2 DM complicated with DR) and this group was further subdivided to subgroup Ia (diabetic patients with proliferative diabetic retinopathy) and subgroup Ib (diabetic patients with nonproliferative diabetic retinopathy); group II (type 2 DM without retinopathy) and group III (apparently healthy subjects representing control group). All subjects were subjected to full medical history taking, physical examination including BMI and blood pressure measurement as well as fundus examination. Fasting and 2 hr post-prandial plasma glucose, HbA1C, serum creatinine and urea, ALT, AST, serum albumin, microalbuminuria as well as plasma PTX3 wereassessed. Results Plasma PTX3 level was significantly higher in diabetic patients with diabetic retinopathy than that in both diabetic patients without diabetic retinopathy and control healthy subjects (3.20 ± 0.035 ng/dl versus 2.88 ± 0.32 ng/dl and 2.88 ± 0.167 ng/dl respectively; P-value =0.000).The Correlation between pentraxin 3 and other measured parameters in all studied subjects showed a statistical positive correlation between log PTX3 and age, duration of diabetes, DBP, FBG, 2HPP, HBA1c, albumin, creatinine, urea, microalbuminuria. Conclusion Serum pentraxin 3 is strongly correlated to diabetic retinopathy and the higher the grade of retinopathy, the higher the pentraxin 3 level. So, pentraxin 3 can be considered a reliable predictor for diabetic retinopathy. Serum pentraxin 3 and diabetic retinopathy are strongly correlated to level of glycaemia and duration of diabetes as well as to creatinine, urea and micro-albuminuria. This draws the attention to the role of tight glycemic control in the prevention or slowing diabetic retinopathy progression and to the relation between diabetic retinopathy and nephropathy.