Background Diabetic macular edema is a major cause of visual loss in patients with diabetes mellitus. Methods This is a clinical interventional, nonrandomized comparative study aimed to investigate the efficacy of intravitreal injection of 4mg (0.1ml) triamcinolone acetonide as primary treatment for chronic diffuse diabetic macular edema. Included in this study were 24 patients, their age ranged from 38-65 years (55.25 +/- 17.94) and the duration of visual deterioration ranged from 8-36 months (21.75 +/- 13.83). As baseline and at the end of the first, third and sixth month(s) follow up periods after injection, assessment of the patients was done functionally and anatomically by measuring the visual acuity (VA), visual evoked potential (VEP) and macular thickness and volume using Optical Cohedence Tomography (OCT). Results Marked improvements were observed at the end of 1-, 3- and 6-months follow up periods. At the end of the first, third and sixth month(s) follow up periods, visual evoked response showed marked improvement in amplitude from initial 7.31 +/- 2.23 to 15.37 +/- 3.88 (P<0.001), 26.69 +/- 3.72 (P<0.001) and 25.65 +/- 2.28 mu V (P<0.001). All patients showed marked improvement in visual acuity. Macular thickness was reduced from initial 375 +/- 35.50 to 233.33 +/- 40.17 (P<0.001), 145.83 +/- 27.58 (P<0.001) and 202.46 +/- 29.60 micron (P<0.01), respectively. Macular volume was reduced from initial 10.39 +/- 1.87 to 7.73 +/- 1.01 (P<0.001), 6.55 +/- 0.99 (P<0.01) and 6.61 +/- 1.09 micron (P<0.01). Intraocular pressure (IOP) was elevated from 13.92 +/- 3.85 to 20.58 +/- 8.42 mmHg (P<0.001) after the first month of injection and decreased significantly to 15.83 +/- 4.15 mmHg and 14.63 +/- 1.46 (P<0.001, P<0.001 and P=NS) at the end of the first, third and sixth months follow up periods. However, 25% of the patients developed recurrence of edema at the end of sixth month and necessitated re-injection. Conclusions We concluded that 1) Intravitreal triamcinolone acetonide is a safe effective primary treatment of diffuse chronic diabetic macular edema, and 2) VEP and OCT are objective practical diagnostic valuable simple techniques for monitoring functional and anatomic improvement following intravitreal corticosteroid injection.