The authors evaluated the effects of biodegradable poly (lactic acid) microspheres that provided the controlled release of the antimetabolic agent adriamycin (ADR) to prevent post surgical fibrosis after glaucoma filtering surgery. Fifty six eyes of 28 rabbits underwent posterior lip sclerotomy and received a 0.2 ml subconjunctival injection that contained microspheres 90 degrees from the filtering site immediately after surgery. Microspheres containing ADR (100 or 200 micrograms) were randomly administered to one eye. The fellow eyes served as controls and received microspheres without the drug. Intraocular pressure in the eyes treated with the microspheres that contained the drug was significantly lower than that in the control eyes from days 7-12 in the 100 micrograms group and from days 6-16 in the 200 micrograms group (P < .05). Eyes that received ADR had a significantly longer patent filtering bleb compared with the control eyes (P < .05). No corneal complications were observed in the eyes treated with 100 micrograms of ADR and the control eyes. Peripheral corneal opacities (25%) and epithelial erosion (17%) were observed in the eyes that received the 200 micrograms dose, but the cornea returned to normal after 4 wk. These results suggest that controlled-drug-release microspheres with an antimetabolic agent may be promising for preventing fibrosis after surgery.