AIM: To determine the efficacy of meloxicam ophthalmic formulation on COX-2 activity and expression, inflammation-related cytokines expression and inflammation in an ocular inflammation model. METHODS: Ocular inflammation was induced in New Zealand rabbits by topical application of croton oil (3%) for 3 h. An ophthalmic solution of 0.03% meloxicam, 0.1% sodium diclofenac or vehicle (Sophisen) was administered every 4 h. Conjunctiva, cornea, aqueous humour and vitreous humour were collected. RESULTS: In irritated eyes, 72 h of meloxicam treatment downregulated COX-2 expression and activity (mRNA by RT-PCR and PGE2 levels by ELISA, respectively) in a time-dependent manner and reduced inflammation. Meanwhile, diclofenac failed to reduce COX-2 mRNA or PGE2 to basal levels after 7 days of treatment. Meloxicam treatment downregulated IL-6 and IFN-gamma expression in the conjunctiva and IL-1beta and TNF-alpha expression in the cornea. Diclofenac failed to modify these cytokines in both tissues. Meloxicam treatment increased the expression of IL-6 in conjunctiva, and IL-10 in cornea, while diclofenac had no effect on these cytokines. CONCLUSION: Meloxicam treatment was more efficient than diclofenac in downregulating the expression and activity of COX-2, reducing inflammation, and modifying the inflammatory-related cytokines.