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Background: Diabetic macular edema (DME) is an important cause of visual impairment in type 2 diabetes. Central macular thickness (CMT) measured using optical coherence tomography (OCT) is a noninvasive method for diagnosis and quantification of DME. OCT not only helps in follow-up and prognosis of macular edema but also aids in early detection of DME, which might not be clinically evident. The study suggests that inflammatory process plays a critical role in retinopathy. C-reactive protein (CRP), an inflammatory marker, is expected to be elevated in patients with poor glycemic control. Furthermore, data on possible association of CRP with diabetic retinopathy are sparse and a limited number of studies reported inconsistent results. The present study is to find the correlation of CRP and glycosylated hemoglobin (HbA1c) on severity of DME. Materials and Methods: This was a case–control study done in a tertiary hospital including 75 cases (type 2 diabetes patients with DME) and 75 controls (diabetics without DME) of diabetic age >5 years. Cases subdivided based on CMT into mild (201–300 μ), moderate (301–400 μ), and severe macular edema (>400 μ). Results: CRP was positive (>0.6 mg/dl) in 32 cases (42.7%) and five controls (6.7%), and positive correlation was obtained between CRP and DME severity. Elevated HbA1c level was associated with increased severity of DME. Conclusion: As inflammation plays a significant role in the pathogenesis of DME, CRP level can be considered as a biomarker to determine the severity of DME along with HbA1c levels.