In this study anti-inflammatory effects of the alpha-melanocyte stimulating hormone (α-MSH) on ocular inflammation caused by extracapsular lens extraction (ECLE) have been investigated and the potential mechanism of an anti-inflammatory effect is discussed. Pigmented rabbit eyes after ECLE were treated locally with α-MSH, dexamethasone, diclofenac, or saline 4 times a day (q.i.d.) for 4 weeks. The inhibitory effect of α-MSH on infiltrating cells in the aqueous humor (AqH) was almost twice as good as that of dexamethasone or diclofenac for 3 days, 1 week, and 2 weeks after the operation. The eyes of Sprague-Dawley rats were treated with an intravenous injection of α-MSH or saline immediately after ECLE. Six hours postoperatively, the iris/ciliary body exhibited increased expression of TNF-α and IL-6 mRNAs, which were significantly decreased after α-MSH treatment. The number of activated NF-kappa B (NFκB)-positive cells in the iris/ciliary body was also significantly reduced by the α-MSH treatment. These results suggested that α-MSH could effectively reduce ocular inflammation after ECLE, and the potential mechanism for this is by down-regulating the expression of proinflammatory cytokines and inhibiting the NFκB-dependent signaling pathway.