Objective To examine the hyperglycemic effects of periocular dexamethasone injection in type 2 diabetic patients after vitreoretinal surgery (VRS). Methods This was a retrospective non-randomized controlled trial. Twenty consecutive hospitalized patients with type 2 diabetes and ocular inflammatory reaction after VRS were enrolled in this study. Ten patients received 2.5 mg dexamethasone and 10 patients received 5 mg dexamethasone. Fourteen consecutive type 2 diabetic patients without ocular inflammatory reaction after VRS were used as control group. We measured fasting blood glucose (FBG) and at 2 h after each meal (post prandial glucose, PBG; 09:00, 13:00, and 19:00 h) after periocular dexamethasone injection. Differences among three groups were determined by q tests. Results The PBG levels in both dexamethasone-treated groups started to increase within 5 h after injection (i.e., PBG at 13:00 h), and were significantly increased at 19:00 h after injection (P<0.05). BG levels were almost 2-fold higher than at baseline and compared with the control group. The BG values declined gradually by 24 h to 48 h after injection. There were no differences in BG levels between the two dexamethasone-treated groups (P>0.05), except for PBG at 19:00 h on day 2 after injection (P<0.05). Conclusion Periocular dexamethasone injection can cause transient hyperglycemia in diabetic patients after VRS. BG monitoring should be performed following such injection.