Systemic use of retinoids is common in the treatment of various dermatological disorders. Blepharitis and conjunctivitis have been reported in 20–45% of the patients following systemic treatment with 13-cis-retinoic acid. Our purpose was to study the histopathological changes in the eyelids caused by long-term systemic treatment of female New Zealand rabbits with isotretinoin (2 mg/kg) and etretinate (2 mg/kg). The histopathological evaluation showed degenerative changes in the meibomian gland acini, leading to cell necrosis and a decrease in the basaloid cells lining the acini walls. No evidence of acute or chronic inflammatory reaction was noted.