Purpose: To compare the effect of topical insulin and sodium hyaluronate in the treatment of epithelial defects secondary to intraoperative corneal epithelial debridement during pars plana vitrectomy in diabetics. Methods: Controlled clinical trial. Patients were randomized to one of three treatment groups: Topical 0.15% sodium hyaluronate (group I), topical insulin 0.5 IU/drop (group II) or combined treatment with topical insulin 0.5 IU/drop and 0.15% sodium hyaluronate (group III). Results: Thirty-six eyes of 36 patients were included, 12 eyes in each group. There were no statistically significant differences in baseline characteristics. The time required until complete re-epithelialization was of 4.25 ± 0.62, 3.0 ± 0.85 and 3.33 ± 0.98 days, in groups I, II and III, respectively; group II showed a significantly shorter reepithelialization time (p < 0.001). All groups had a reduction in the area of the epithelial defect from day 1; a smaller area was observed in group II; however, this difference was not statistically significant. No adverse effects were reported. Conclusions: Both topical insulin and combined treatment with topical insulin and sodium hyaluronate are effective to treat corneal epithelial defects secondary to intraoperative corneal epithelial debridement during pars plana vitrectomy in diabetics. The addition of sodium hyaluronate to topical insulin did not provide a greater benefit. The three treatments were safe and well tolerated.