While in Nuremberg, Merian wrote the first volume of her two-volume book Caterpillars, Their Wondrous Transformation and Peculiar Nourishment from Flowers (or simply The Caterpillar Book). Merian depicted moths and butterflies in various stages of metamorphosis, the process by which they transform from egg to caterpillar to adult. Each image was organized around a single plant and was accompanied by a text in which Merian described the colors, forms, and timing of each stage of transformation. By including the caterpillars' food sources in her natural history illustrations, Merian brought a more ecological approach to the study of metamorphosis.

Merian's work helped to disprove the common belief that insects reproduced by spontaneous generation from decaying matter such as old meat or rotten fruit, and her aesthetic sensitivity raised the standards of scientific illustration.