Sub-Tenon or subconjunctival administration of carboplatin is used to consolidate tumor regression by achieving high intraocular concentrations, without incurring systemic toxicity, in selected patients with intraocular retinoblastoma. Mild transient periocular edema is a common side effect of this treatment. We describe four patients with severe local soft-tissue toxic reaction mimicking preseptal cellulitis following subtenon carboplatin injections. The development of this complication after injecting through the inferior conjunctiva and unexpectedly severe signs are the unusual features of these patients. We did not encounter this complication after injections through the superior conjunctiva in 22 other patients using the same technique and identical drug dosage.