Diabetic macular edema(DME) is a major sight-threatening cause in diabetic patients. We review the long-term outcome of four approved pharmacotherapy for treating DME, including intravitreal injections of corticosteroids(dexamethasone implants and fluocinolone acetonide inserts) and anti-vascular endothelial growth factor(VEGF)(ranibizumab and aflibercept). They all show superior ability to improve vision and reduce macular thickness, comparing with sham injections or macular focal/grid laser treatment. Anti-VEGF agents result in low incidence of severe ocular or systemic adverse effects, but glaucoma and cataract should be aware after intravitreal corticosteroids. Prompt treatment with these agents can lead to a better outcome. We review the long-term outcome of four approved pharmacotherapy for treating DME, including intravitreal injections of corticosteroids (dexamethasone implants and fluocinolone acetonide inserts) and anti-vascular endothelial growth factor (VEGF) (ranibizumab and aflibercept). They all show superior ability to improve vision and reduce macular thickness, comparing with sham injections or macular focal / grid laser treatment. Anti-VEGF agents result in low incidence of severe ocular or systemic adverse effects, but glaucoma and cataract should be aware after intravitreal corticosteroids. Prompt treatment with these agents can lead to a better outcome.