A lens epithelial (LE) cell cDNA clone, designatedClone 156, was isolated from a mature rat LE cDNA library by methods of subtractive hybridization. The cDNA sequence ofClone 156was 521 nucleotides in length, excluding the poly(T)-tail, and it encoded an open reading frame of 115 amino acids. The translated protein shared extensive sequence similarities with macrophage migration inhibitory factor (MIF) from mouse lens and human T-cell lymphocytes. Northern blot hybridization showed that rat lens MIF mRNA is about 500 nucleotides in length and that its expression in mature rat lens is relatively low in comparison with that in other rat tissues. The expression of MIF mRNA in LE of normal rats and of rats treated by feeding a diet of 50% (w/w) galactose was studied by quantitative RT-PCR. The results showed that the expression of MIF mRNA in a 20-day galactosemic rat LE increased twelvefold as compared to that found in control LE. From the results of this study and from what we know about the locale of epithelial cell differentiation in mature rat lenses, it is being proposed that the increase in abundance of MIF mRNA in the cataractous rat lens is correlated with the enhanced proliferation of the undifferentiated epithelial cells.