In this paper, we reviewed our recent works on a possible link between molecular evolution and tissue evolution. The evolutionary rates of genes that are expressed tissue specifically were shown to differ widely to one another, depending on tissues: Brain specific genes evolve with significantly slower rate than immune specific genes. The tissue dependence of molecular evolutionary rate strongly suggests the presence of functional constraints against molecular changes from tissue level. A molecular phylogenetic analysis of tissue specific isoforms that are identical to one another in function, but differ only in tissue distribution revealed frequent gene duplications and rapid accumulations of amino acid substitutions during the early evolution of chordates, where rapid evolution at the tissue or organ levels is thought to have occurred. On the basis of functional constraints, a possible explanation for the correlation between evolution at the two levels was presented.